Endocrinology and Metabolism

Original Article

Association of Multiple Obesity-Related Composite Indices with All-Cause Mortality in Patients with Stage 0–3 Cardiovascular-Kidney-Metabolic Syndrome: Jianmin Lu, Jiajin Yang, Zhuoyi Peng, Cilu Huang, Yue Chen, Chuanzhao Zhang, Baohua Hou, Xiaoqing He, Shanzhou Huang; Received October 14, 2025 Accepted December 31, 2025 Published online May 7, 2026; DOI: https://doi.org/10.3803/EnM.2025.2711 [Epub ahead of print]

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Abstract PDF: Background
This study aimed to determine the predictive ability of eight composite obesity-related indices for all-cause mortality in adults with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3, given the inadequacy of conventional anthropometric measures.
Methods
We conducted a prospective cohort study using UK Biobank data, including 261,742 adults with CKM stages 0–3 at baseline. Eight indices (body mass index, relative fat mass [RFM], body roundness index [BRI], lipid accumulation product [LAP], visceral adiposity index, cardiometabolic index [CMI], atherogenic index of plasma, and triglyceride-glucose index) were evaluated using multivariable logistic regression, Cox proportional hazards models, receiver operating characteristic analysis, and restricted cubic spline (RCS) modeling to examine their associations with, and predictive ability for, all-cause mortality.
Results
During follow-up, 13,437 deaths (5.1%) occurred. All eight indices were positively associated with mortality (P<0.001). BRI was the strongest predictor (area under the curve [AUC]=0.658; optimal cutoff=4.515), outperforming LAP (AUC=0.616) and CMI (AUC=0.610). RFM exhibited the lowest discriminative ability (AUC=0.502). Higher quartiles of most indices were associated with progressively increased mortality risk, with BRI demonstrating consistent predictive value across subgroups in RCS analyses.
Conclusion
BRI showed the strongest and most consistent association with all-cause mortality in CKM stages 0–3, suggesting that it may act as a robust tool for early risk stratification and support targeted prevention strategies.

Review Articles

Mineral, bone & muscle
Beyond Weight Loss: Skeletal Considerations in Obesity Treatment: Myung Jin Kim, Yun Kyung Cho; Endocrinol Metab. 2026;41(2):210-221. Published online April 8, 2026; DOI: https://doi.org/10.3803/EnM.2026.2986

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The rapid evolution of obesity therapeutics, led by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metabolic surgery, has achieved unprecedented weight loss. However, the skeletal consequences of such substantial weight reduction are of increasing clinical concern. This review explores the relationship between obesity, weight-loss modalities, and bone health. While obesity was historically viewed as bone-protective due to mechanical loading, recent evidence highlights qualitative bone deterioration and sitespecific fracture risks. Intentional weight loss through caloric restriction or bariatric surgery consistently accelerates bone turnover and reduces bone mineral density (BMD), with surgical interventions showing the most significant impact. Emerging data on GLP-1RAs suggest modest BMD declines, largely proportional to weight loss and likely driven by mechanical unloading. Conversely, preclinical studies indicate that GLP-1 signaling may exert direct osteoanabolic and anti-resorptive effects. To preserve skeletal integrity, obesity management must shift toward a holistic body composition framework. Integrating structured resistance exercise, optimizing nutrition (calcium, vitamin D, and protein), and implementing skeletal monitoring in high-risk individuals are essential. Future obesity care should prioritize the maintenance of bone quality and lean mass alongside fat reduction to ensure long-term skeletal resilience and prevent fragility fractures.

Citations

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Association Between Lifestyle Factors and the Prevalence of Non-Communicable Diseases in Saudi Adults Across Different Age Groups: A Cross-Sectional Study
Somia A. Nassar
Diseases.2026; 14(5): 163. CrossRef

Miscellaneous Big Data Articles (National Health Insurance Service Database)
Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions: Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2026;41(1):86-104. Published online February 26, 2026; DOI: https://doi.org/10.3803/EnM.2026.2953

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The Korean National Health Information Database (NHID) is a large-scale dataset created through linkage of National Health Insurance claims with nationwide health screening records. Because it is released in a cohort-based format, the NHID enables longitudinal follow-up and allows investigation of rare endocrine conditions with low population prevalence. Mortality data, including both dates and causes of death, are additionally obtained through linkage with Statistics Korea. Over recent years, use of the NHID has expanded rapidly, establishing it as a major resource for epidemiological research in endocrinology. Nevertheless, because the database was originally developed for administrative and screening purposes rather than for research, investigators face several methodological limitations, particularly the need to construct and validate robust operational definitions of diseases. In this review, we describe the key features of the Korean NHID, summarize operational definitions of endocrine disorders that have been applied in prior research, and provide an overview of recent endocrine studies conducted using this database.

Citations

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Age-specific loss of life expectancy after hip fracture in Asian adults: A nationwide population-based cohort study
Kyoung Jin Kim, Su Jin Kwon, Seunghyun Lee, Seong Hee Ahn, So Young Park, Ha-Young Kim, Kyoung Min Kim
Bone.2026; 208: 117896. CrossRef

Original Article

GYG1 as a Dual Biomarker of Glucagon-Like Peptide-1 Receptor Agonist Weight-Loss Response: Findings from an Integrative Multi-Omics Substudy of a Phase II Trial: Lijun Li, Mengyu Hou, Qiannan Gao, Liyuan Zhao, Ruihua Dong; Received September 3, 2025 Accepted October 22, 2025 Published online February 4, 2026; DOI: https://doi.org/10.3803/EnM.2025.2641 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The global obesity crisis requires precision biomarkers to overcome treatment resistance. We investigated circulating multi-omics signatures for predicting and monitoring glucagon-like peptide-1 receptor agonist (GLP-1RA) (GZR18) response, addressing gaps in personalized obesity therapy.
Methods
We conducted longitudinal multi-omics profiling (proteomics, metabolomics, and lipidomics) of 221 plasma samples from 25 participants (n=25) treated with GZR18 at nine time points over 30 weeks (four samples could not be tested due to hemolysis). High-resolution mass spectrometry quantified molecular features alongside clinical body mass index (BMI) trajectories. Theil-Sen regression modeled baseline predictors (BMI slope Z), while linear regression analysis identified longitudinal biomarkers (%BMI change). Significant candidates (P<0.05) underwent gene set enrichment analysis (GSEA; Kyoto Encyclopedia of Genes and Genomes [KEGG] pathways) and STRING network integration, with dual-response biomarkers validated through correlation and trajectory analyses.
Results
GZR18-treated obese patients exhibited a dose-dependent reduction in BMI, with 48 mg biweekly producing the steepest declines (Z<–0.4 vs. placebo: Z=–0.22, P<0.001). We identified glycogenin 1 (GYG1) as a dual-function biomarker (coefficient=2.0 for prediction, P<0.05 for monitoring) and as a central network hub. Lipidomic (phosphatidylinositol 18:2–18:2) and metabolomic (oxoglutaric acid) markers predicted baseline response, while proteomic (insulin like growth factor binding protein 2 [IGFBP2]) and lipidomic (phosphatidylcholine 18:0–20:3) profiles tracked longitudinal efficacy (P<0.05). Adipocytokine signaling governed the initial response (normalized enrichment score >1.8), while starch/sucrose metabolism modulated ongoing efficacy through integrated molecular networks.
Conclusion
This study establishes GYG1 as a clinically actionable, dual-function biomarker for GLP-1RA therapy in obesity, linking baseline prediction and real-time monitoring of treatment response through integrated multi-omics profiling. Our findings highlight convergent metabolic pathways driving therapeutic efficacy and provide a precision-medicine framework for optimizing obesity pharmacotherapy through blood-based molecular signatures.

Review Article

Diabetes, obesity and metabolism
From Old to New: A Comprehensive Review of Obesity Diagnostic Criteria and Their Implications: Sangmo Hong, Cheol-Young Park; Endocrinol Metab. 2025;40(4):517-522. Published online August 20, 2025; DOI: https://doi.org/10.3803/EnM.2025.2590

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Obesity is a chronic, multifactorial disease that imposes significant health burdens worldwide. Although body mass index (BMI) is widely used for its simplicity and utility at the population level, it fails to capture critical clinical aspects, including body composition, fat distribution, metabolic health, and functional impairment. This review explores the limitations of current BMI-based diagnostic criteria for obesity and introduces a new definition and diagnostic framework proposed by the Commission on Clinical Obesity. The new criteria redefine obesity using clinical and biological markers and distinguish between clinical and preclinical obesity based on functional consequences and risk stratification. This approach aims to facilitate more accurate diagnoses, individualized treatment, and evidence-based health policies, while also addressing issues such as weight stigma and overdiagnosis. Further research is needed to validate this model and support its integration into clinical practice.

Citations

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BMI-stratified phenotypes of polycystic ovary syndrome: advances in gut microbiota research and personalized management strategies
Bisha Su, Yining Cao, Lin Ma, Jian Huang
Frontiers in Endocrinology.2026;[Epub] CrossRef
Association of regional fat distribution indicators with infertility in women: insights from the 2013–2018 NHANES
Luming Chen, Fangxiang Mu, Tianyu He, Fang Wang
Gynecological Endocrinology.2026;[Epub] CrossRef
Muscle Insulin Resistance Elicits Muscle Atrophy in Obesity
Omid Razi, Nastaran Zamani, Ayoub Saeidi, Marios Hadjicharalambous, Khadija Ayed, Anthony C. Hackney, Juan Del Coso, Ismail Laher, Giovanna Muscogiuri, Hassane Zouhal
Current Obesity Reports.2025;[Epub] CrossRef
Beyond BMI: Rethinking Obesity Metrics and Cardiovascular Risk in the Era of Precision Medicine
Maria-Daniela Tanasescu, Andrei-Mihnea Rosu, Alexandru Minca, Andreea-Liana Rosu, Maria-Mihaela Grigorie, Delia Timofte, Dorin Ionescu
Diagnostics.2025; 15(23): 3025. CrossRef

Original Article

Diabetes, obesity and metabolism
Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model: Shih-Chang Hsu, Ching-Lu Chen, Chung Te Liu, Hung-Chieh Lo, Ying-Kuo Liu, Pei-Song Gao, Shau-Ku Huang, Chin-Wang Hsu; Endocrinol Metab. 2026;41(1):108-120. Published online August 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2360

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Abstract PDF Supplementary Material PubReader ePub: Background
Type 2 diabetes mellitus (T2DM) is increasingly prevalent and frequently associated with obesity, insulin resistance, nonalcoholic fatty liver disease, and chronic kidney disease. Emerging evidence suggests sphingosine-1-phosphate (S1P), a bioactive sphingolipid, plays a significant role in the pathogenesis of T2DM. This study aimed to investigate how reduced S1P levels impact T2DM development.
Methods
S1P lyase knock-in (S1PL^C317A KI) mice, characterized by reduced S1P levels due to impaired S1P degradation, were compared with wild-type (WT) mice. Both groups were fed a high-fat diet (HFD) to induce T2DM. Parameters including body weight, insulin resistance, blood glucose levels, hepatic fat accumulation, and kidney pathology were evaluated. Next-generation sequencing was employed to identify differentially expressed genes.
Results
S1PL^C317A KI mice exhibited greater body weight, more pronounced insulin resistance, and higher blood glucose levels compared to WT mice on an HFD. Increased hepatic fat deposition and worsened diabetic kidney disease were also observed in KI mice. Sequencing analysis identified 4,656 differentially expressed genes, notably enriched in mitochondrial and bioenergetic pathways, including 133 diabetes-related genes.
Conclusion
Reduced S1P levels exacerbate T2DM symptoms, indicating that therapeutic targeting of S1P pathways may offer promising strategies for treating T2DM and its related complications.

Review Article

Diabetes, obesity and metabolism
Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024: Eun-Jung Rhee; Endocrinol Metab. 2025;40(2):174-184. Published online April 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2398

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Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.

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So Hyun Cho, Seohyun Kim, Rosa Oh, Ji Yoon Kim, Myunghwa Jang, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
Diabetologia.2026; 69(3): 653. CrossRef
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2024 Cardio-cerebrovascular disease fact sheet in Korea
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Miguel A. Arce-Huamani, Gustavo A. Caceres-Cuellar, Anyela Y. Guevara-Paz, Cleofe R. Lopez-Quispe, Abhely K. Barzola-Blancas, Valeria A. Cespedes-Atto, Catherine G. Acosta-Celis, Katherine Pérez-Acuña, Williams Carrascal-Astola, J. Smith Torres-Roman
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Yejin Kim, Hong Ji Song, Dong-Hyun Kim, Jin-Young Jeong, Kyung Hee Park, Jwa-Kyung Kim, Hye-Mi Noh
Scientific Reports.2025;[Epub] CrossRef

Original Article

Diabetes, obesity and metabolism
Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons: Sujin Yoo, Eun-Seon Yoo, Jae Il Kim, Jong-Woo Sohn; Endocrinol Metab. 2025;40(3):434-447. Published online April 14, 2025; DOI: https://doi.org/10.3803/EnM.2024.2185

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Background
Glucagon-like peptide-1 (GLP-1) is an incretin known for its anti-obesity effects, and several effective drugs targeting GLP-1 receptors (GLP-1Rs) have recently been developed to treat obesity. Although GLP-1Rs are expressed by various populations of central neurons, it is still unclear which specific populations mediate the anti-obesity effects of GLP-1R agonists.
Methods
In this study, we utilized the previously reported GLP-1R agonist, exendin-4(1-32)K-capric acid (Ex-4c), and conducted whole-cell patch-clamp recordings, immunohistochemistry experiments, and in vivo food intake measurements.
Results
Our findings indicate that the appetite-suppressing effects of Ex-4c depend on pro-opiomelanocortin (POMC) neurons. Fos immunochemistry experiments and whole-cell patch-clamp recordings showed that Ex-4c activated POMC neurons in the arcuate nucleus of the hypothalamus. Additionally, we observed that Ex-4c stimulated GLP-1Rs and activated the protein kinase A (PKA)- dependent signaling pathway, which in turn closed putative adenosine triphosphate-sensitive K⁺ (K_ATP) channels, leading to the depolarization of POMC neurons.
Conclusion
Our results demonstrate that the appetite-suppressing effects of Ex-4c are mediated through the activation of arcuate POMC neurons. Furthermore, the PKA-dependent closure of putative K_ATP conductance is identified as the cellular mechanism responsible for the activation of POMC neurons.

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Hypothalamic regulation of sepsis-associated anorexia: cytokine and hormonal signalling through AgRP/POMC circuits
Wanting Zhu, Claude Libert, Tineke Vanderhaeghen
EMBO Molecular Medicine.2026;[Epub] CrossRef
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Wenwen Yang, Nan Pang, Xiaoxia He
Lipids in Health and Disease.2025;[Epub] CrossRef
Glucagon-Like Peptide-1 Receptor Agonists Are Promising for the Treatment of Brain Diseases: an Outlook from the Perspective of Integrative Physiology
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Journal of Evolutionary Biochemistry and Physiology.2025; 61(5): 1326. CrossRef

Brief Report

Diabetes, obesity and metabolism
Association of Steatotic Liver Disease with Retinal Vascular Occlusion: The Influence of Obesity in a Large Health Screening Cohort: Younjin Oh, Su Jeong Song; Endocrinol Metab. 2025;40(2):299-303. Published online February 12, 2025; DOI: https://doi.org/10.3803/EnM.2024.2181

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Abstract PDF Supplementary Material PubReader ePub: In this cross-sectional study, we aimed to investigate the relationship between steatotic liver disease (SLD) and retinal abnormalities in a cohort undergoing health screening. Our study included 353,607 participants who underwent fundus photography and abdominal ultrasonography at least once at the Kangbuk Samsung Health Promotion Center from 2002 to 2022. After adjusting for age and sex, the risk of retinal vein occlusion (RVO) significantly increased with the presence of non-alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, and metabolic dysfunction-associated SLD, with odds ratios of 1.259 (95% confidence interval [CI], 1.050 to 1.510), 1.498 (95% CI, 1.249 to 1.796), and 1.342 (95% CI, 1.121 to 1.605), respectively. However, these associations weakened after adjusting for body mass index. No statistically significant associations were observed with other retinal disorders after adjusting for age, sex, and other confounding factors. Our findings suggest that obesity may mediate the relationship between SLD and RVO, while other retinal abnormalities may be more closely associated with known risk factors rather than SLD itself.

Original Articles

Diabetes, obesity and metabolism
Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra; Endocrinol Metab. 2025;40(1):112-124. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164

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Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

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Tirzepatide and Obesity: A Narrative Review
Arya Singh, Rahnuma Ahmad, Kona Chowdhury, Mahendra Narwaria, Mainul Haque
Advances in Human Biology.2026; 16(2): 290. CrossRef
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Endocrinology, Diabetes & Metabolism.2026;[Epub] CrossRef
Glucagon-like peptide 1 receptor agonists and cancer risk: the good, the bad and the unknown
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Incretin-Based Therapy and Thyroid Cancer Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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AACE Endocrinology and Diabetes.2026;[Epub] CrossRef
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Testimony Ipaye, Jonathan Goldney, Thomas J. Wilkinson, Francesco Zaccardi, Thomas Yates, Melanie J. Davies, Karen Brown, Dimitris Papamargaritis
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GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research
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Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk: Nawoda Hewage, Udaya Wijesekara, Rasika Perera; Endocrinol Metab. 2024;39(6):864-876. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2015

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Background
We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

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Increased Serum Lipopolysaccharide Levels are Related to a Higher Prevalent Risk of Subclinical Hypothyroidism
Xuan An, Xiaoyi Wang, Jin Zhang, Mingtong Xu, Muchao Wu, Suraiya Saleem
International Journal of Endocrinology.2025;[Epub] CrossRef
Incidence of Subclinical Hypothyroidism in Obese Adults and Its Metabolic Implications: A Prospective Cohort Study
Umer Jameel, Obaidullah Durrani, Ahmad Munib, Amanullah Khan
Cureus.2025;[Epub] CrossRef

Review Articles

Diabetes, obesity and metabolism
Epidemiology and Trends of Obesity and Bariatric Surgery in Korea: Kyungdo Han, Jin-Hyung Jung, Su-Min Jeong, Mee Kyoung Kim; Endocrinol Metab. 2024;39(5):678-685. Published online August 2, 2024; DOI: https://doi.org/10.3803/EnM.2024.2056

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The prevalence of obesity in Korea has steadily increased over the past decade, reaching 38.4% in 2021. Notably, the rate of class II– III obesity, defined as a body mass index (BMI) of 30 kg/m² or higher, exceeded 7% in the same year. Since January 2019, the National Health Insurance Service (NHIS) has provided coverage for bariatric surgery (BS) for eligible patients. Coverage is available for individuals with a BMI of 35 kg/m² or higher, or those with a BMI of 30 kg/m² or higher who also have obesity-related comorbidities. Additionally, partial reimbursement is offered for BS in patients with type 2 diabetes mellitus who have BMI values between 27.5 and 30 kg/m². From 2019 to 2022, the NHIS recorded 9,080 BS procedures, with sleeve gastrectomy being the most commonly performed. The average percentage of weight loss 198±99.7 days post-surgery was 17.9%, with 80.0% of patients losing more than 10% of their body weight. This article presents the trends in obesity and BS in Korea.

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Diabetes, obesity and metabolism
Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management: Jang Won Son, Soo Lim; Endocrinol Metab. 2024;39(2):206-221. Published online April 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1940

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Obesity is a significant risk factor for health issues like type 2 diabetes and cardiovascular disease. It often proves resistant to traditional lifestyle interventions, prompting a need for more precise therapeutic strategies. This has led to a focus on signaling pathways and neuroendocrine mechanisms to develop targeted obesity treatments. Recent developments in obesity management have been revolutionized by introducing novel glucagon-like peptide-1 (GLP-1) based drugs, such as semaglutide and tirzepatide. These drugs are part of an emerging class of nutrient-stimulated hormone-based therapeutics, acting as incretin mimetics to target G-protein–coupled receptors like GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon. These receptors are vital in regulating body fat and energy balance. The development of multiagonists, including GLP-1–glucagon and GIP–GLP-1–glucagon receptor agonists, especially with the potential for glucagon receptor activation, marks a significant advancement in the field. This review covers the development and clinical efficacy of various GLP-1-based therapeutics, exploring the challenges and future directions in obesity management.

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Diabetes, obesity and metabolism
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update: Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen; Endocrinol Metab. 2024;39(1):12-22. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1942

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Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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Miscellaneous
Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer: Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park; Endocrinol Metab. 2023;38(6):619-630. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1814

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Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

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Diabetes, obesity and metabolism
The Impact of Taurine on Obesity-Induced Diabetes Mellitus: Mechanisms Underlying Its Effect: Kainat Ahmed, Ha-Neul Choi, Jung-Eun Yim; Endocrinol Metab. 2023;38(5):482-492. Published online October 17, 2023; DOI: https://doi.org/10.3803/EnM.2023.1776

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This review explores the potential benefits of taurine in ameliorating the metabolic disorders of obesity and type 2 diabetes (T2D), highlighting the factors that bridge these associations. Relevant articles and studies were reviewed to conduct a comprehensive analysis of the relationship between obesity and the development of T2D and the effect of taurine on those conditions. The loss of normal β-cell function and development of T2D are associated with obesity-derived insulin resistance. The occurrence of diabetes has been linked to the low bioavailability of taurine, which plays critical roles in normal β-cell function, anti-oxidation, and anti-inflammation. The relationships among obesity, insulin resistance, β-cell dysfunction, and T2D are complex and intertwined. Taurine may play a role in ameliorating these metabolic disorders through different pathways, but further research is needed to fully understand its effects and potential as a therapeutic intervention.

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Original Article

Diabetes, obesity and metabolism
Protective Effects of Melatonin in High-Fat Diet-Induced Hepatic Steatosis via Decreased Intestinal Lipid Absorption and Hepatic Cholesterol Synthesis: Hyungjune Ku, Yeonji Kim, Alvin Lyle Kim, Garam Lee, Youngsik Choi, Bukyung Kim; Endocrinol Metab. 2023;38(5):557-567. Published online September 1, 2023; DOI: https://doi.org/10.3803/EnM.2023.1672

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Background
The preventative effect of melatonin on the development of obesity and the progression of fatty liver under a high-fat diet (HFD) has been well elucidated through previous studies. We investigated the mechanism behind this effect regarding cholesterol biosynthesis and regulation of cholesterol levels.
Methods
Mice were divided into three groups: normal chow diet (NCD); HFD; and HFD and melatonin administration group (HFD+M). We assessed the serum lipid profile, mRNA expression levels of proteins involved in cholesterol synthesis and reabsorption in the liver and nutrient transporters in the intestines, and cytokine levels. Additionally, an in vitro experiment using HepG2 cells was performed.
Results
Expression of hepatic sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) demonstrated that melatonin administration significantly reduces hepatic cholesterol synthesis in mice fed an HFD. Expression of intestinal sodium-glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), GLUT5, and Niemann-pick C1-like 1 (NPC1L1) demonstrated that melatonin administration significantly reduces intestinal carbohydrate and lipid absorption in mice fed an HFD. There were no differences in local and circulatory inflammatory cytokine levels among the NCD, HFD, and HFD+M group. HepG2 cells stimulated with palmitate showed reduced levels of SREBP, LDLR, and HMGCR indicating these results are due to the direct mechanistic effect of melatonin on hepatocytes.
Conclusion
Collectively, these data indicate the mechanism behind the protective effects of melatonin from weight gain and liver steatosis under HFD is through a reduction in intestinal caloric absorption and hepatic cholesterol synthesis highlighting its potential in the treatment of obesity and fatty liver disease.

Citations

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Sleep Deprivation Exacerbates High‐Fat Diet‐Induced Obesity and MAFLD Through Melatonin Reduction Mediated NF‐κB Activation
Renjiao Liu, Yiping Zhou, Chongyang Wei, Xincheng Wang, Huiyu Hao, Lifeng Wang, Yakun Ma, Yi Wang, Chunjun Li, Dongyan Chen
Journal of Pineal Research.2026;[Epub] CrossRef
Lipid metabolism-MAFLD crosstalk: mechanisms and therapy
Bojia Li, Shengai Piao, Yin Fu, Qiang Fu, Peiyao Qin, Weitai Kong, Yidi Ma, Zhe Zhang, Xue Fang, Xiaoyang Hu
Frontiers in Endocrinology.2026;[Epub] CrossRef
Melatonin Prevents the Progression of MASLD via Inhibiting FFAs-Induced Ferroptosis through KEAP1/NRF2/HO-1 Pathway
Shuojiao Li, Peng Rao, Wenxian Yu, Yue Tang, Xuanpeng Jiang, Jiatao Liu
Biomolecules & Therapeutics.2025; 33(5): 876. CrossRef
Effect of melatonin on adipokines, biochemical parameters, clock genes, and lipid metabolism in a rat obesity model
Héctor Edmundo Álvarez-Loredo, Esther Layseca-Espinosa, Claudia Inés Victoria-Campos, Héctor Hernández-Mendoza, Estefanía Chávez-Prieto, María Judith Rios-Lugo
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Melatonin in the pathogenesis and treatment of metabolic liver diseases
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Review Article

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database: Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2023;38(1):10-24. Published online February 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.102

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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

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Original Articles

Diabetes, Obesity and Metabolism
Sleep Duration and the Risk of Type 2 Diabetes: A Community-Based Cohort Study with a 16-Year Follow-up: Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Seung Ku Lee, Chol Shin, Nan Hee Kim; Endocrinol Metab. 2023;38(1):146-155. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1582

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Background
We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians.
Methods
We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hours/night, >5 to 7 hours/night (reference), and >7 hours/night. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex.
Results
During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 h/night had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hours/night group in non-obese individuals, men, and those aged <60 years, and in the >7 hours/night group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively).
Conclusion
This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

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Diabetes, Obesity and Metabolism
Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults: Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee; Endocrinol Metab. 2022;37(5):781-790. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1532

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Background
Shift work is associated with obesity and metabolic syndrome. However, this association in the normal-weight population remains unclear. This study aimed to investigate whether shift work is associated with normal-weight obesity (NWO).
Methods
From the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset (2008 to 2011), 3,800 full-time workers aged ≥19 years with a body mass index (BMI) ≤25 kg/m² were analysed. We defined NWO as BMI ≤25 kg/m² and body fat percentage ≥25% in men and ≥37% in women. Working patterns were classified into “daytime,” “other than daytime,” and “shift.” Multivariable logistic regression analysis was performed to evaluate the relationship between shift work and NWO.
Results
Shift work was associated with higher odds of NWO than daytime work (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.04 to 2.09) and night/evening work (aOR, 1.87; 95% CI, 1.11 to 3.14) after adjustment for type of work, working hours, age, sex, BMI, 25-hydroxyvitamin D levels, homeostatic model assessment for insulin resistance, and other sociodemographic factors. In subgroup analyses, the association between shift work and NWO was more robust in those aged ≥60 years and those working ≥56 hours/week.
Conclusion
Shift work was associated with NWO in community-dwelling Korean adults, independent of age, sex, BMI, and other covariates.

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Antonino De Lorenzo, Paola Gualtieri, Giulia Frank, Roselisa Palma, Rossella Cianci, Leonardo Romano, Lucilla Ciancarella, Glauco Raffaelli, Laura Di Renzo
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Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging: Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn; Endocrinol Metab. 2022;37(4):630-640. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1430; Correction in: Endocrinol Metab 2025;40(4):657

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Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

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Ping-Ping Zhang, Gao-Feng Lin, Jia-Ying Gu, Bi-Lian Wang, Jie Zhang, Ye Zhou, Miao Xu, Hui Wang, Li Li
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Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty
KAYLONI OLSON, DENISE K. HOUSTON, JOHNATHAN ROSS, RENA R. WING, FELICIA R. SIMPSON, AMBARISH PANDEY, MICHAEL P. WALKUP, MIA YANG, MARK A. ESPELAND
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Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
Biochimica et Biophysica Acta (BBA) - General Subjects.2023; 1867(2): 130281. CrossRef
Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
Jaime A. Gallo-Villegas, Juan C. Calderón
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Diabetes, Obesity and Metabolism
Association between the Blautia/Bacteroides Ratio and Altered Body Mass Index after Bariatric Surgery: Yoonhong Kim, Dooheon Son, Bu Kyung Kim, Ki Hyun Kim, Kyung Won Seo, Kyoungwon Jung, Seun Ja Park, Sanghyun Lim, Jae Hyun Kim; Endocrinol Metab. 2022;37(3):475-486. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1481; Correction in: Endocrinol Metab 2022;37(4):701

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Background
Current evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery.
Methods
Between January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m², n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m², n=41) were investigated.
Results
The gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI.
Conclusion
In the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.

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Diabetes, Obesity and Metabolism
Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017: Moon Young Seo, Shinje Moon, Shin-Hye Kim, Mi Jung Park; Endocrinol Metab. 2022;37(2):249-260. Published online April 7, 2022; DOI: https://doi.org/10.3803/EnM.2021.1235

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Background
Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

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Diabetes, Obesity and Metabolism
Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors: Yong-Jik Lee, Yoo-Na Jang, Hyun-Min Kim, Yoon-Mi Han, Hong Seog Seo, Youngsub Eom, Jong-suk Song, Ji Hoon Jeong, Tae Woo Jung; Endocrinol Metab. 2022;37(2):221-232. Published online March 23, 2022; DOI: https://doi.org/10.3803/EnM.2021.1237

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Background
Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.
Methods
To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.
Results
Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.
Conclusion
The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

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Namgok Lecture 2021

Diabetes, Obesity and Metabolism
The Influence of Obesity and Metabolic Health on Vascular Health: Eun-Jung Rhee; Endocrinol Metab. 2022;37(1):1-8. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.101

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The prevalence of obesity is rapidly increasing worldwide. Obesity should not be understood only as the accumulation of fat in the body, but instead as a phenomenon that exerts different effects on our health according to the place of fat deposition and its stability. Obesity is the starting point of most metabolic diseases, such as diabetes, hypertension, metabolic syndrome, sleep apnea, and eventually cardiovascular disease. There are different kinds of obesity, ranging from simple obesity to sarcopenic obesity. The main purpose of intervening to address obesity is to decrease the ultimate consequence of obesity—namely, cardiovascular disease. The main mechanism through which obesity, especially abdominal obesity, increases cardiovascular risk is the obesity-induced derangement of metabolic health, leading to the development of metabolic diseases such as diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, which are the main initiators of vascular damage. In this review, I discuss the influence of various types of obesity on the risk of metabolic diseases, and how these diseases increase cardiovascular disease risk.

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Original Articles

Diabetes, Obesity and Metabolism
The Leg Fat to Total Fat Ratio Is Associated with Lower Risks of Non-Alcoholic Fatty Liver Disease and Less Severe Hepatic Fibrosis: Results from Nationwide Surveys (KNHANES 2008–2011): Hyun Min Kim, Yong-ho Lee; Endocrinol Metab. 2021;36(6):1232-1242. Published online November 23, 2021; DOI: https://doi.org/10.3803/EnM.2021.1087

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Background
The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea.
Methods
This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used.
Results
The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis.
Conclusion
A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

Citations

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Kuan-Yu Lai, Chun-Yi Wang, Hsian-Han Kao, Wen-Yuan Lin, Tsung-Po Chen
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Low leg fat mass is associated with low insulin sensitivity, inflammatory markers, and β-cell dysfunction in non-obese Japanese people
Satomi Minato-Inokawa, Mari Honda, Ayaka Tsuboi-Kaji, Mika Takeuchi, Kaori Kitaoka, Miki Kurata, Bin Wu, Tsutomu Kazumi, Keisuke Fukuo
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cardiovascular Outcomes of Obesity According to Menopausal Status: A Nationwide Population-Based Study: Bo Kyung Koo, Sang-Hyun Park, Kyungdo Han, Min Kyong Moon; Endocrinol Metab. 2021;36(5):1029-1041. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1197

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Background
We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status.
Methods
Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559).
Results
In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women.
Conclusion
The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

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Diabetes, Obesity and Metabolism
Prognostic Value of Triglyceride and Glucose Index for Incident Type 2 Diabetes beyond Metabolic Health and Obesity: Hwi Seung Kim, Jiwoo Lee, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Hong-Kyu Kim, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung; Endocrinol Metab. 2021;36(5):1042-1054. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1184

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Background
Metabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index.
Methods
The study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group.
Results
During the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively.
Conclusion
MHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

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Diabetes, Obesity and Metabolism
Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability: Inha Jung, Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(4):845-854. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1098

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Background
Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.
Methods
We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.
Results
On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).
Conclusion
Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

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Impact of Change, Fluctuation, or Variability in Weight on the Risk of Nonalcoholic Fatty Liver Disease in General Population: A Systematic Review and Meta‐Analysis
Dorsa Alijanzadeh, Masoud Noroozi, Negin Rostami, Narges Norouzkhani, Mahdie ShojaeiBaghini, Saeed Zivari Lashkajani, Ali Mirzaei, Maryam Dianati, Maryam Salimi, Hamidreza Sadeghsalehi, Faezeh Jadidian, Sajjad Ghane Ezabadi, Mohammad Sadegh Fallahi, Mobin
Health Science Reports.2025;[Epub] CrossRef
Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model
Anouk Charlot, Anthony Bringolf, Léa Debrut, Joris Mallard, Anne-Laure Charles, Emilie Crouchet, Delphine Duteil, Bernard Geny, Joffrey Zoll
Nutrients.2024; 16(5): 646. CrossRef
Body weight variability and the risk of liver‐related outcomes in type 2 diabetes and steatotic liver disease: a cohort study
Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
Obesity.2024; 32(6): 1210. CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
A machine-learned model for predicting weight loss success using weight change features early in treatment
Farzad Shahabi, Samuel L. Battalio, Angela Fidler Pfammatter, Donald Hedeker, Bonnie Spring, Nabil Alshurafa
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Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish
Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen
International Journal of Molecular Sciences.2024; 25(23): 13225. CrossRef
Weight variability, physical functioning and incident disability in older adults
Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(4): 1648. CrossRef
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinology and Metabolism.2022; 37(1): 74. CrossRef
Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
Obesity.2022; 30(6): 1279. CrossRef
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
Nature Reviews Gastroenterology & Hepatology.2022; 19(10): 638. CrossRef
Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
Nutrients.2022; 14(14): 2795. CrossRef
Higher Weight Variability Could Bring You a Fatty Liver
Yeoree Yang, Jae-Hyoung Cho
Endocrinology and Metabolism.2021; 36(4): 766. CrossRef
Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
Frontiers in Endocrinology.2021;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism: Ju Hee Lee, Saet-Byel Jung, Seong Eun Lee, Ji Eun Kim, Jung Tae Kim, Yea Eun Kang, Seul Gi Kang, Hyon-Seung Yi, Young Bok Ko, Ki Hwan Lee, Bon Jeong Ku, Minho Shong, Hyun Jin Kim; Endocrinol Metab. 2021;36(3):661-671. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.1023

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Background
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPR^mt) in adipose tissue is associated with obesity in humans and rodents.
Methods
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

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The role and mechanism of UPRmt in adipocytes
Hao Liu, Jie Chen, Dan-Qi Qiu, Miao-Wei Jiang, Hao-Qi Chen, Li Li, Shu-Qin Chen
Adipocyte.2026;[Epub] CrossRef
Enhanced mitochondrial biogenesis facilitates the development of cutaneous squamous cell carcinoma
Ziyang Wang, Ke He, Meng Liu, Weiqiang Lv, Baochen Cheng, Guanfei Zhang, Xueqiang Wang, Mengqi Zeng, Lianying Jiao, Shujun Han, Yan Zheng, Zhihui Feng
Cancer Letters.2025; 618: 217623. CrossRef
LONP1 facilitates pulmonary artery smooth muscle cell glycolytic reprogramming by degrading MPC1 in pulmonary hypertension
Mingkang Li, Wenkang Zhang, Minhao Zhang, Linqing Li, Yuyu Yao, Yuhan Qin, Dong Wang, Gaoliang Yan, Yong Qiao, Chengchun Tang
Clinical Science.2025; 139(10): 479. CrossRef
LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure
Muchen Wu, Jing Wu, Kai Liu, Minjie Jiang, Fang Xie, Xuehong Yin, Jushan Wu, Qinghua Meng
Chinese Medical Journal.2024; 137(2): 190. CrossRef
Tissue‐specific roles of mitochondrial unfolded protein response during obesity
Fernanda S. Carneiro, Carlos K. Katashima, Joshua D. Dodge, Dennys E. Cintra, José Rodrigo Pauli, Adelino S. R. Da Silva, Eduardo R. Ropelle
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Mitochondrial quality control proteases and their modulation for cancer therapy
Jiangnan Zhang, Wenliang Qiao, Youfu Luo
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Effects of Obesity and Calorie Restriction on Cancer Development
Ekaterina Sergeeva, Tatiana Ruksha, Yulia Fefelova
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Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity
Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Natalia Gazatova, Larisa Litvinova
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Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome
Yuan Xie, Shuwen Chen, Zaixin Guo, Ying Tian, Xinyu Hong, Penghui Feng, Qiu Xie, Qi Yu
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Diabetes, Obesity and Metabolism
Efficacy and Safety of the New Appetite Suppressant, Liraglutide: A Meta-Analysis of Randomized Controlled Trials: Shinje Moon, Jibeom Lee, Hye Soo Chung, Yoon Jung Kim, Jae Myung Yu, Sung Hoon Yu, Chang-Myung Oh; Endocrinol Metab. 2021;36(3):647-660. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2020.934

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Background
Obesity is a chronic disease associated with metabolic diseases such as diabetes and cardiovascular disease. Since the U.S. Food and Drug Administration approved liraglutide as an anti-obesity drug for nondiabetic patients in 2014, it has been widely used for weight control in overweight and obese people. This study aimed to systematically analyze the effects of liraglutide on body weight and other cardiometabolic parameters.
Methods
We investigated articles from PubMed, EMBASE, and the Cochrane Library to search randomized clinical trials that examined body weight changes with liraglutide treatment.
Results
We included 31 studies with 8,060 participants for this meta-analysis. The mean difference (MD) between the liraglutide group and the placebo group was −4.19 kg (95% confidence interval [CI], −4.84 to −3.55), with a −4.16% change from the baseline (95% CI, −4.90 to −3.43). Liraglutide treatment correlated with a significantly reduced body mass index (MD: −1.55; 95% CI, −1.76 to −1.34) and waist circumference (MD: −3.11 cm; 95% CI, −3.59 to −2.62) and significantly decreased blood pressure (systolic blood pressure, MD: −2.85 mm Hg; 95% CI, −3.36 to −2.35; diastolic blood pressure, MD: −0.66 mm Hg; 95% CI, −1.02 to −0.30), glycated hemoglobin (MD: −0.40%; 95% CI, −0.49 to −0.31), and low-density lipoprotein cholesterol (MD: –2.91 mg/dL; 95% CI, −5.28 to −0.53; MD: −0.87% change from baseline; 95% CI, −1.17 to −0.56).
Conclusion
Liraglutide is effective for weight control and can be a promising drug for cardiovascular protection in overweight and obese people.

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Review Articles

Obesity and Metabolism
Food Preferences and Obesity: Sara Spinelli, Erminio Monteleone; Endocrinol Metab. 2021;36(2):209-219. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2021.105

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Obesity is a multifactorial disease with several potential causes that remain incompletely understood. Recent changes in the environment, which has become increasingly obesogenic, have been found to interact with individual factors. Evidence of the role of taste responsiveness and food preference in obesity has been reported, pointing to a lower taste sensitivity and a higher preference and intake of fat and, to a lesser extent, sweet foods in obese people. Studies in the last decades have also suggested that individual differences in the neurophysiology of food reward may lead to overeating, contributing to obesity. However, further studies are needed to confirm these findings. In fact, only a limited number of studies has been conducted on large samples, and several studies were conducted only on women. Larger balanced studies in terms of sex/gender and age are required in order to control the confounding effect of these variables. As many factors are intertwined in obesity, a multidisciplinary approach is needed. This will allow a better understanding of taste alteration and food behaviours in obese people in order to design more effective strategies to promote healthier eating and to prevent obesity and the related chronic disease risks.

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Obesity and Metabolism
An Update on Contraception in Polycystic Ovary Syndrome: Seda Hanife Oguz, Bulent Okan Yildiz; Endocrinol Metab. 2021;36(2):296-311. Published online April 15, 2021; DOI: https://doi.org/10.3803/EnM.2021.958

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Abstract PDF PubReader ePub

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.

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Obesity and Metabolism
Digital Therapeutics for Obesity and Eating-Related Problems: Meelim Kim, Hyung Jin Choi; Endocrinol Metab. 2021;36(2):220-228. Published online March 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.107

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528 Download
25 Web of Science
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Abstract PDF PubReader ePub

In recent years, digital technologies have rapidly advanced and are being applied to remedy medical problems. These technologies allow us to monitor and manage our physical and mental health in our daily lives. Since lifestyle modification is the cornerstone of the management of obesity and eating behavior problems, digital therapeutics (DTx) represent a powerful and easily accessible treatment modality. This review discusses the critical issues to consider for enhancing the efficacy of DTx in future development initiatives. To competently adapt and expand public access to DTx, it is important for various stakeholders, including health professionals, patients, and guardians, to collaborate with other industry partners and policy-makers in the ecosystem.

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Clinical Evaluation of Digital Therapeutics: Present and Future
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Sigrídur Lára Gudmundsdóttir, Tommaso Ballarini, María L. Ámundadóttir, Judit Mészáros, Jenna H. Eysteinsdóttir, Ragna H. Thorleifsdóttir, Sigrídur K. Hrafnkelsdóttir, Heida B. Bragadóttir, Saemundur Oddsson, Jonathan I. Silverberg
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Brief Report

Obesity and Metabolism
Overweight and Obesity are Risk Factors for Coronavirus Disease 2019: A Propensity Score-Matched Case-Control Study: Wonjun Ji, Rugyeom Lee, Kyungmin Huh, Minsun Kang, In Cheol Hwang, Munkhzul Radnaabaatar, Dae Ho Lee, Jaehun Jung; Endocrinol Metab. 2021;36(1):196-200. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.856

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Although obesity is a risk factor for infection, whether it has the same effect on coronavirus disease 2019 (COVID-19) need confirming. We conducted a retrospective propensity score matched case-control study to examine the association between obesity and COVID-19. This study included data from the Nationwide COVID-19 Registry and the Biennial Health Checkup database, until May 30, 2020. We identified 2,231 patients with confirmed COVID-19 and 10-fold-matched negative test controls. Overweight (body mass index [BMI] 23 to 24.9 kg/m²; adjusted odds ratio [aOR], 1.16; 95% confidence interval [CI], 1.1.03 to 1.30) and class 1 obesity (BMI 25 to 29.9 kg/m²; aOR, 1.27; 95% CI, 1.14 to 1.42) had significantly increased COVID-19 risk, while classes 2 and 3 obesity (BMI ≥30 kg/m²) showed similar but non-significant trend. Females and those <50 years had more robust association pattern. Overweight and obesity are possible risk factors of COVID-19.

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Original Articles

Endocrine Research
Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice: Dae Hyun Kim, Ye Ra Kim, EunJin Bang, Sugyeong Ha, Sang Gyun Noh, Byeong Moo Kim, Seong Ho Jeong, Hee Jin Jung, Ji Young Lee, Hae Young Chung; Endocrinol Metab. 2021;36(1):171-184. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.850

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Background
Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated.
Methods
To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD).
Results
Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups.
Conclusion
Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.

Citations

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Relationship between hepatic lipid accumulation and type 2 diabetes mellitus
Zhe Wang, Wang Zan, Zhe Fan, Shuang Wang
Biomedicine & Pharmacotherapy.2025; 193: 118723. CrossRef
β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model
Peng Zhang, Naicheng Liu, Mingyang Xue, Mengjie Zhang, Zidong Xiao, Chen Xu, Yuding Fan, Junqiang Qiu, Qinghua Zhang, Yong Zhou
Animals.2024; 14(9): 1289. CrossRef
Par2-mediated responses in inflammation and regeneration: choosing between repair and damage
Gal Reches, Ron Piran
Inflammation and Regeneration.2024;[Epub] CrossRef
Betaine Suppresses Lipid Accumulation in Liver: Inhibition of FoxO6 and PPARγ Interaction
Min Hi Park, Dae Hyun Kim
Journal of Medicinal Food.2024; 27(12): 1231. CrossRef
Biochanin‐A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF‐β1 and PAR‐2 genes expression in kidney tissues of STZ‐induced diabetic rats
Jamal Amri, Mona Alaee, Rasool Babaei, Zahra Salemi, Reza Meshkani, Ali Ghazavi, Ahmad Akbari, Mehdi Salehi
Biotechnology and Applied Biochemistry.2022; 69(5): 2112. CrossRef
Delineation of the healthy rabbit liver by immunohistochemistry – A technical note
Gabriella Meier Bürgisser, Olivera Evrova, Dorothea M. Heuberger, Julia Rieber, Pietro Giovanoli, Maurizio Calcagni, Johanna Buschmann
Acta Histochemica.2021; 123(7): 151795. CrossRef

Endocrine Research
Danshen Extracts Prevents Obesity and Activates Mitochondrial Function in Brown Adipose Tissue: Yoon Hee Cho, Cheol Ryong Ku, Young-Suk Choi, Hyeon Jeong Lee, Eun Jig Lee; Endocrinol Metab. 2021;36(1):185-195. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.835

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Background
Danshen has been widely used in oriental medicine to improve body function. The purpose of this study is to investigate the effect of water-soluble Danshen extract (DE) on weight loss and on activation proteins involved in mitochondrial biogenesis in brown adipose tissue (BAT) in obese mice.
Methods
BAT was isolated from 7-week-old male Sprague-Dawley rats, and expression of proteins related to mitochondrial biogenesis was confirmed in both brown preadipocytes and mature brown adipocytes treated with DE. For the in vivo study, low-density lipoprotein receptor knock out mice were divided into three groups and treated for 17 weeks with: standard diet; high fat diet (HFD); HFD+DE. Body weight was measured every week, and oral glucose tolerance test was performed after DE treatment in streptozotocin-induced diabetic mice. To observe the changes in markers related to thermogenesis and adipogenesis in the BAT, white adipose tissue (WAT) and liver of experimental animals, tissues were removed and immediately frozen in liquid nitrogen.
Results
DE increased the expression of uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in brown preadipocytes, and also promoted the brown adipocyte differentiation and mitochondrial function in the mature brown adipocytes. Reactive oxygen species production in brown preadipocytes was increased depending on the concentration of DE. DE activates thermogenesis in BAT and normalizes increased body weight and adipogenesis in the liver due to HFD. Browning of WAT was increased in WAT of DE treatment group.
Conclusion
DE protects against obesity and activates mitochondrial function in BAT.

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Salvia miltiorrhiza components and gut microbiota interactions in Helicobacter pylori infection
Shao-jian Li, Jin-xin Miao, Fei Wang, Hao-yu Wang, Yao-wu Ma, Ying Jiang, Xia Xue
Journal of Integrative Medicine.2025; 23(5): 462. CrossRef
Pharmacological Benefits and Underlying Mechanisms of Salvia miltiorrhiza against Molecular Pathology of Various Liver Diseases: A Review
Cho Hyun Hwang, Eungyeong Jang, Jang-Hoon Lee
The American Journal of Chinese Medicine.2023; 51(07): 1675. CrossRef

Clinical Study
Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity: Suji Yoo, Jaehoon Jung, Hosu Kim, Kyoung Young Kim, Soo Kyoung Kim, Jungwha Jung, Jong Ryeal Hahm, Jong Ha Baek; Endocrinol Metab. 2020;35(4):873-881. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.798

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Background
To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity.
Methods
In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index.
Results
During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable.
Conclusion
Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Citations

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Metabolic indexes of obesity in major depressive disorders in different age groups
Jieyu Zhou, Yukang Tan, Shasha Huang, Yajie Zhang, Jiaquan Liang
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Kate Meads, Pranav Machiraju, Yumeng Shi, Stephen Colagiuri
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Jung-Hwan Kim, Yaeji Lee, Chung-Mo Nam, Yu-Jin Kwon, Ji-Won Lee
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Endocrine Research
Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer: Seonhyang Jeong, In-Kyu Kim, Hyunji Kim, Moon Jung Choi, Jandee Lee, Young Suk Jo; Endocrinol Metab. 2020;35(3):656-668. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.667

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Background
Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features.
Methods
Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort.
Results
In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets.
Conclusion
The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

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Rui Liang, Guofeng Zhang, Wenhua Xu, Weibing Liu, Youjia Tang
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Lyndsey A. Reich, Ana S. Leal, Edmund Ellsworth, Karen T. Liby
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Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer
Seonhyang Jeong, Seul-Gi Lee, Hyunji Kim, Gibbeum Lee, Sunmi Park, In-Kyu Kim, Jandee Lee, Young-Suk Jo
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Mian Liu, Rooh Afza Khushbu, Pei Chen, Hui-Yu Hu, Neng Tang, Deng-jie Ou-yang, Bo Wei, Ya-xin Zhao, Peng Huang, Shi Chang
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Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment
Lisha Bao, Tong Xu, Xixuan Lu, Ping Huang, Zongfu Pan, Minghua Ge
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Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer
Seonhyang Jeong, Seul Gi Lee, Hyunji Kim, Gibbeum Lee, Sunmi Park, In-Kyu Kim, Jandee Lee, Young Suk Jo
International Journal of Thyroidology.2021; 14(2): 152. CrossRef

Review Article

Obesity and Metabolism
Metabolically Healthy and Unhealthy Normal Weight and Obesity: Norbert Stefan; Endocrinol Metab. 2020;35(3):487-493. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.301

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Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

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Original Articles

Endocrine Research
Serotonin Regulates De Novo Lipogenesis in Adipose Tissues through Serotonin Receptor 2A: Ko Eun Shong, Chang-Myung Oh, Jun Namkung, Sangkyu Park, Hail Kim; Endocrinol Metab. 2020;35(2):470-479. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.470; Correction in: Endocrinol Metab 2020;35(3):672

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Background
Obesity is defined as excessive fat mass and is a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer. Increasing energy expenditure and regulating adipose tissue metabolism are important targets for the treatment of obesity. Serotonin (5-hydroxytryptophan [5-HT]) is a monoamine metabolite of the essential amino acid tryptophan. Here, we demonstrated that 5-HT in mature adipocytes regulated energy expenditure and lipid metabolism.
Methods
Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme during 5-HT synthesis in non-neural peripheral tissues. We generated adipose tissue-specific Tph1 knockout (Tph1 FKO) mice and adipose tissue-specific serotonin receptor 2A KO (Htr2a FKO) mice and analyzed their phenotypes during high-fat diet (HFD) induced obesity.
Results
Tph1 FKO mice fed HFD exhibited reduced lipid accumulation, increased thermogenesis, and resistance to obesity. In addition, Htr2a FKO mice fed HFD showed reduced lipid accumulation in white adipose tissue and resistance to obesity.
Conclusion
These data suggest that the inhibition of serotonin signaling might be an effective strategy in obesity.

Citations

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Clinical Study
Effect of Lactobacillus sakei, a Probiotic Derived from Kimchi, on Body Fat in Koreans with Obesity: A Randomized Controlled Study: Soo Lim, Ji Hye Moon, Chol Min Shin, Dahye Jeong, Bongjoon Kim; Endocrinol Metab. 2020;35(2):425-434. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.425

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Background
The increased prevalence of obesity has led to increases in the prevalence of chronic diseases worldwide. There is interest whether probiotics have an effect on obesity, but the effectiveness and safety of only a few probiotics for the treatment of obesity have been reported. The purpose of this study was to investigate whether ingestion of Lactobacillus sakei (CJLS03) derived from kimchi causes weight loss in people with obesity.
Methods
This randomized, double-blind, placebo-controlled, clinical trial involved 114 adults with a body mass index (BMI) ≥25 kg/m² who were assigned randomly to a CJLS03 or placebo group. The groups received two allocations of either 5×10⁹ colony-forming units of CJLS03/allocation or the equivalent vehicle for 12 weeks. Demographic and biochemical parameters, and body composition including fat and muscle mass were measured at baseline and after 12 weeks. Changes in body fat, weight, and waist circumference were compared between the two treatment groups. Adverse events were monitored during study period.
Results
Body fat mass decreased by 0.2 kg in the CJLS03 group and increased by 0.6 kg in the placebo group (0.8 kg difference, P=0.018). After the 12 weeks, waist circumference was 0.8 cm smaller in the CJLS03 group than in the placebo group (P=0.013). BMI and body weight did not change after the 12 weeks. Adverse events were mild and did not differ between the two groups.
Conclusion
These data suggest that L. sakei (CJLS03) might help people with obesity reduce body fat mass without serious side effects (ClinicalTrials.gov: NCT03248414).

Citations

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Clinical Study
Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study: Ji Cheol Bae, Nam H. Cho, Jae Hyeon Kim, Kyu Yeon Hur, Sang-Man Jin, Moon-Kyu Lee; Endocrinol Metab. 2020;35(2):416-424. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.416

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Abstract PDF Supplementary Material PubReader ePub

Background
Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population.
Methods
The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox’s proportional hazard analysis.
Results
The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m²). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m² in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m² (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI <21 kg/m²).
Conclusion
These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases.

Citations

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Endocrine Journal.2026; 73(2): 183. CrossRef
Predicting Metabolic and Cardiovascular Healthy from Nutritional Patterns and Psychological State Among Overweight and Obese Young Adults: A Neural Network Approach
Geovanny Genaro Reivan Ortiz, Laura Maraver-Capdevila, Roser Granero
Nutrients.2025; 17(16): 2651. CrossRef
Association of obesity with cardiovascular disease in the absence of traditional risk factors
Hui Luo, Yesong Liu, Xue Tian, Yuhan Zhao, Lulu Liu, Zemeng Zhao, Lili Luo, Yanmin Zhang, Xiaozhong Jiang, Yeqiang Liu, Yanxia Luo, Anxin Wang
International Journal of Obesity.2024; 48(2): 263. CrossRef
Clinical characteristics and degree of cardiovascular risk factor control in patients with newly-diagnosed type 2 diabetes in Catalonia
Anna Ramírez-Morros, Josep Franch-Nadal, Jordi Real, Queralt Miró-Catalina, Magdalena Bundó, Bogdan Vlacho, Didac Mauricio
Frontiers in Endocrinology.2024;[Epub] CrossRef
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Advances in Clinical Medicine.2024; 14(04): 1941. CrossRef
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Ichiro Tatsuno, Laetitia Gerlier, Anamaria-Vera Olivieri, James Baker-Knight, Mark Lamotte
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PLOS ONE.2023; 18(8): e0289749. CrossRef
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Yaying Chen, Mengqian Guan, Ruiqi Wang, Xuewen Wang
Frontiers in Endocrinology.2023;[Epub] CrossRef
Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality
Yoon-Jong Bae, Sang-Jun Shin, Hee-Taik Kang
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Clinical Study
Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer: Hyemi Kwon, Se Eun Park, Ji-Sup Yun, Cheol-Young Park; Endocrinol Metab. 2020;35(2):396-406. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.396

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Background
Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated.
Methods
We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated.
Results
The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 μg/mL and 101.5 ng/mL in the benign group and 5.4 μg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively).
Conclusion
Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

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Review Article

Diabetes
Prevalence and Current Management of Cardiovascular Risk Factors in Korean Adults Based on Fact Sheets: Eun-Jung Rhee; Endocrinol Metab. 2020;35(1):85-94. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.85

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Korea is currently an aged society and is on the cusp of becoming a superaged society in a few years. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. In 2018, the prevalence of obesity in Korea was 35.7% (men, 45.4%; women, 26.5%) according to the Obesity Fact Sheet 2019, based on National Health Insurance Corporation medical checkup data. In 2016, the prevalence of diabetes was 14.4% in Koreans older than 30 years according to the Diabetes Fact Sheet published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2018 was 28.3% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2018 was 40.5% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations.

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Original Articles

Clinical Study
Associations of Perirenal Fat Thickness with Renal and Systemic Calcified Atherosclerosis: Bo Kyung Koo, Julie O. Denenberg, C. Michael Wright, Michael H. Criqui, Matthew A. Allison; Endocrinol Metab. 2020;35(1):122-131. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.122

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Background

We investigated associations between perirenal fat thickness and atherosclerotic calcification in six different vascular beds.

Methods

Using a community-based cohort (n=3,919), perirenal fat thickness was estimated from computed tomography scans. It was classified as Q1 (the lowest quartile) to Q4 (the highest quartile) in each sex. Calcification in the carotid arteries, coronary arteries, thoracic aorta, abdominal aorta, iliac arteries, and renal arteries was evaluated.

Results

Perirenal fat thickness was associated with older age (P<0.01) and a higher prevalence of obesity, hypertension, and dyslipidemia (P<0.01 for all). Perirenal fat thickness was independently associated with renal arterial calcification even after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking history, and family history of heart diseases in first-degree relatives (odds ratio [OR] per quartile of perirenal fat thickness, 1.25; 95% confidence interval [CI], 1.09 to 1.44). Compared to Q1, the odds of renal arterial calcification in Q4 was about two times higher (OR, 2.05; 95% CI, 1.29 to 3.25). After adjustment for renal arterial calcification and atherosclerotic risk factors, the only other vascular bed where perirenal fat thickness showed a significant association with calcification was the abdominal aorta (OR, 1.11; 95% CI, 1.00 to 1.23; P=0.045).

Conclusion

Perirenal fat thickness was independently associated with vascular calcification in the renal artery and abdominal aorta.

Citations

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Association between perirenal fat tissue thickness and subclinical atherosclerosis in patients newly diagnosed with type 2 diabetes: a cross-sectional study
Işıl Isel, Mehmet Karagulle, Turgut Karabag
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Ana Checa-Ros, Antonella Locascio, Owahabanun-Joshua Okojie, Pablo Abellán-Galiana, Luis D’Marco
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Clinical Study
Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study: Jung A Kim, Da Hye Kim, Seon Mee Kim, Yong Gyu Park, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi, Kyungdo Han, Hye Jin Yoo; Endocrinol Metab. 2019;34(4):406-414. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.406

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Background

Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.

Methods

We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.

Results

During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain.

Conclusion

Metabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index.

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Review Article

Obesity and Metabolism
Implications of Mitochondrial Unfolded Protein Response and Mitokines: A Perspective on Fatty Liver Diseases: Hyon-Seung Yi; Endocrinol Metab. 2019;34(1):39-46. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.39

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The signaling network of the mitochondrial unfolded protein response (UPR^mt) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPR^mt is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPR^mt and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPR^mt and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

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Original Article

Obesity and Metabolism
Distinct Ultradian Rhythms in Plasma Clusterin Concentrations in Lean and Obese Korean Subjects: Jong Han Choi, Eunheui Jeong, Byung Soo Youn, Min-Seon Kim; Endocrinol Metab. 2018;33(2):245-251. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.245

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Background

Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men.

Methods

For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period.

Results

Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues.

Conclusion

These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.

Citations

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Telma Quintela, André Furtado, Ana C. Duarte, Isabel Gonçalves, Jihwan Myung, Cecília R.A. Santos
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Review Article

Metabolic Surgery in Korea: What to Consider before Surgery: Mi-Kyung Kim, Yoonseok Heo; Endocrinol Metab. 2017;32(3):307-315. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.307

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Obesity is increasing globally and represents a significant global health problem because it predisposes towards various diseases, such as type 2 diabetes mellitus, cardiovascular disease, degenerative joint disease, and certain types of cancer. Numerous studies have shown that bariatric surgery reduces body mass and ameliorates obesity-related complications, such as hypertension and hyperglycemia, suggesting that surgery is the most effective therapeutic option for severely obese and obese diabetic patients. Recent international guidelines recommend surgical treatment for diabetic patients with class III obesity (body mass index [BMI] >40 kg/m²), regardless of their level of glycemic control or the complexity of their glucose-lowering regimens, and for patients with class II obesity (BMI 35.0 to 39.9 kg/m²) and hyperglycemia that is poorly controlled despite appropriate lifestyle and pharmacological therapy. The most popular procedures are Roux-en-Y gastric bypass and sleeve gastrectomy, but new procedures with better outcomes have been reported. For optimal surgical outcome, comprehensive management including assessments of a medical condition, nutrition, mental health, and social support is needed before and after surgery. However, there is still a lack of understanding regarding metabolic surgery in Korea. Therefore, this article reviews indications for metabolic surgery in patients with a specific focus on the situation in Korea.

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