Endocrinology and Metabolism

Original Articles

Calcium & bone metabolism
Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019): Seong Hee Ahn, Eun Byeol Park, Seongha Seo, Yongin Cho, Da Hea Seo, So Hun Kim, Young Ju Suh, Seongbin Hong; Endocrinol Metab. 2023;38(6):709-719. Published online November 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1740

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Abstract PDF Supplementary Material PubReader ePub: Background
The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults.
Methods
This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability.
Results
The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69–3.10; P=0.027–0.038), especially in daughters (OR, 2.04–4.64; P=0.029–0.034).
Conclusion
HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Calcium & bone metabolism
Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults: Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim; Endocrinol Metab. 2023;38(6):701-708. Published online October 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1783

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Abstract PDF Supplementary Material PubReader ePub: Background
Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.
Methods
This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.
Results
After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012).
Conclusion
These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Miscellaneous
Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study: Tae Kyung Yoo, Marie Yung-Chen Wu, Moon Soo Kim, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park; Endocrinol Metab. 2023;38(2):269-276. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1588

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Abstract PDF PubReader ePub: Background
Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted.
Methods
We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (−2 standard deviation [SD] < SMI ≤−1 [SD]), and severely LMM groups (SD ≤−2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors.
Results
This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89).
Conclusion
Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Miscellaneous
DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation: Sudeep Kumar, Jonghwa Jin, Hyeon Young Park, Mi-Jin Kim, Jungwook Chin, Sungwoo Lee, Jina Kim, Jung-Guk Kim, Yeon-Kyung Choi, Keun-Gyu Park; Endocrinol Metab. 2022;37(5):800-809. Published online September 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1462

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Background
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods
VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results
DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion
Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.

Citations

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Jatrorrhizine inhibits Piezo1 activation and reduces vascular inflammation in endothelial cells
Tianying Hong, Xianmei Pan, Han Xu, Zhijuan Zheng, Lizhen Wen, Jing Li, Mingfeng Xia
Biomedicine & Pharmacotherapy.2023; 163: 114755. CrossRef

Review Article

Diabetes, Obesity and Metabolism
Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research: Ji-Hoon Kim, Seung-Min Yu, Jang Won Son; Endocrinol Metab. 2022;37(3):408-414. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.302

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Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle, which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discuss the future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.

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Human‐based new approach methodologies to accelerate advances in nutrition research
Manuela Cassotta, Danila Cianciosi, Maria Elexpuru‐Zabaleta, Inaki Elio Pascual, Sandra Sumallo Cano, Francesca Giampieri, Maurizio Battino
Food Frontiers.2024;[Epub] CrossRef
Key indicators of beef safety and quality as important aspects of conservation
S. V. Furman, I. M. Sokulskyi, D. V. Lisohurska, O. V. Lisohurska, B. V. Gutyj
Ukrainian Journal of Veterinary and Agricultural Sciences.2024; 7(1): 68. CrossRef

Brief Report

Diabetes, Obesity and Metabolism
Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle: Min Jeong Park, Joo Won Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo; Endocrinol Metab. 2022;37(3):552-557. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1421

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Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.

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Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation
Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye
Clinical and Experimental Hypertension.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
Frontiers in Endocrinology.2023;[Epub] CrossRef

Original Articles

Calcium & Bone Metabolism
Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia: Seong Hee Ahn, Hee-Won Jung, Eunju Lee, Ji Yeon Baek, Il-Young Jang, So Jeong Park, Jin Young Lee, Eunah Choi, Yun Sun Lee, Seongbin Hong, Beom-Jun Kim; Endocrinol Metab. 2022;37(3):487-496. Published online May 27, 2022; DOI: https://doi.org/10.3803/EnM.2022.1428

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Background
Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia.
Methods
Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay.
Results
The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025).
Conclusion
Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

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Zhonghan Zhao, Kai Yan, Qiao Guan, Qiang Guo, Can Zhao
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Viktoria N. Karetnikova, Anastasiya G. Neeshpapa, Evgenia I. Carpova, Olga L. Barbarash
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Carina O. Walowski, Catrin Herpich, Janna Enderle, Wiebke Braun, Marcus Both, Mario Hasler, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal
Scientific Reports.2023;[Epub] CrossRef
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Anika Shimonty, Lynda F. Bonewald, Fabrizio Pin
Current Osteoporosis Reports.2023; 21(3): 303. CrossRef
The role of sclerostin in lipid and glucose metabolism disorders
Hewen Jiang, Dijie Li, Ying Han, Nanxi Li, Xiaohui Tao, Jin Liu, Zongkang Zhang, Yuanyuan Yu, Luyao Wang, Sifan Yu, Ning Zhang, Huan Xiao, Xin Yang, Yihao Zhang, Ge Zhang, Bao-Ting Zhang
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Liu Guo, Menchus Quan, Weijun Pang, Yulong Yin, Fengna Li
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Sclerostin: clinical insights in muscle–bone crosstalk
Antimo Moretti, Giovanni Iolascon
Journal of International Medical Research.2023;[Epub] CrossRef
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Giovanni Iolascon, Sara Liguori, Marco Paoletta, Giuseppe Toro, Antimo Moretti
Therapeutic Advances in Musculoskeletal Disease.2023;[Epub] CrossRef
Sclerostin as a Putative Myokine in Sarcopenia
Hyon-Seung Yi
Endocrinology and Metabolism.2022; 37(3): 430. CrossRef
Organokines, Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise
Giulia Minniti, Letícia Maria Pescinini-Salzedas, Guilherme Almeida dos Santos Minniti, Lucas Fornari Laurindo, Sandra Maria Barbalho, Renata Vargas Sinatora, Lance Alan Sloan, Rafael Santos de Argollo Haber, Adriano Cressoni Araújo, Karina Quesada, Jesse
International Journal of Molecular Sciences.2022; 23(21): 13452. CrossRef

Calcium & Bone Metabolism
Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults: Jae-Hyeong Choi, Jin-Woo Seo, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park; Endocrinol Metab. 2022;37(2):333-343. Published online February 8, 2022; DOI: https://doi.org/10.3803/EnM.2021.1202

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Background
Homocysteine has been drawing attention with a closed linkage with skeletal muscle. However, the association of hyperhomocysteinemia with decreased skeletal muscle mass remains unclear. We aimed to investigate the association of hyperhomocysteinemia with low skeletal muscle mass (LMM) in asymptomatic adults.
Methods
This was a cross-sectional study of 114,583 community-dwelling adults without cancer, stroke, or cardiovascular diseases who underwent measurements of plasma homocysteine and body composition analysis from 2012 to 2018. Hyperhomocysteinemia was defined as >15 μmol/L. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)². Participants were classified into three groups based on SMI: “normal,” “mildly low,” and “severely low.”
Results
The prevalence of hyperhomocysteinemia was the highest in subjects with severely LMM (12.9%), followed by those with mildly LMM (9.8%), and those with normal muscle mass (8.5%) (P for trend <0.001). In a multivariable logistic regression model, hyperhomocysteinemia was significantly associated with having a mildly LMM (odds ratio [OR], 1.305; 95% confidence interval [CI], 1.224 to 1.392) and severely LMM (OR, 1.958; 95% CI, 1.667 to 2.286), respectively. One unit increment of log-transformed homocysteine was associated with 1.360 and 2.169 times higher risk of having mildly LMM and severely LMM, respectively.
Conclusion
We demonstrated that elevated homocysteine has an independent association with LMM in asymptomatic adults, supporting that hyperhomocysteinemia itself can be a risk for decline in skeletal musculature.

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Review Article

Miscellaneous
Quality Matters as Much as Quantity of Skeletal Muscle: Clinical Implications of Myosteatosis in Cardiometabolic Health: Hong-Kyu Kim, Chul-Hee Kim; Endocrinol Metab. 2021;36(6):1161-1174. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1348

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Although age-related changes in skeletal muscles are closely associated with decreases in muscle strength and functional decline, their associations with cardiometabolic diseases in the literature are inconsistent. Such inconsistency could be explained by the fact that muscle quality—which is closely associated with fatty infiltration of the muscle (i.e., myosteatosis)—is as important as muscle quantity in cardiometabolic health. However, muscle quality has been less explored compared with muscle mass. Moreover, the standard definition of myosteatosis and its assessment methods have not been established yet. Recently, some techniques using single axial computed tomography (CT) images have been introduced and utilized in many studies, as the mass and quality of abdominal muscles could be measured opportunistically on abdominal CT scans obtained during routine clinical care. Yet, the mechanisms by which myosteatosis affect metabolic and cardiovascular health remain largely unknown. In this review, we explore the recent advances in the assessment of myosteatosis and its changes associated with aging. We also review the recent literature on the clinical implication of myosteatosis by focusing on metabolic and cardiovascular diseases. Finally, we discuss the challenges and unanswered questions that need addressing to set myosteatosis as a therapeutic target for the prevention or treatment of cardiometabolic diseases.

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Assessment of Muscle Quantity, Quality and Function
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Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients
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Original Articles

Calcium & Bone Metabolism
Comparison of Two DXA Systems, Hologic Horizon W and GE Lunar Prodigy, for Assessing Body Composition in Healthy Korean Adults: Seung Shin Park, Soo Lim, Hoyoun Kim, Kyoung Min Kim; Endocrinol Metab. 2021;36(6):1219-1231. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1274

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Background
Dual-energy X-ray absorptiometry (DXA) is the most widely used method for evaluating muscle masses. The aim of this study was to investigate the agreement between muscle mass values assessed by two different DXA systems.
Methods
Forty healthy participants (20 men, 20 women; age range, 23 to 71 years) were enrolled. Total and regional body compositional values for fat and lean masses were measured consecutively with two DXA machines, Hologic Horizon and GE Lunar Prodigy. Appendicular lean mass (ALM) was calculated as the sum of the lean mass of four limbs.
Results
In both sexes, the ALM values measured by the GE Lunar Prodigy (24.8±4.3 kg in men, 15.8±2.9 kg in women) were significantly higher than those assessed by Hologic Horizon (23.0±4.0 kg in men, 14.8±3.2 kg in women). Furthermore, BMI values or body fat (%), either extremely higher or lower levels, contributed greater differences between two systems. Bland-Altman analyses revealed a significant bias between ALM values assessed by the two systems. Linear regression analyses were performed to develop equations to adjust for systematic differences (men: Horizon ALM [kg]=0.915×Lunar Prodigy ALM [kg]+0.322, R²=0.956; women: Horizon ALM [kg]=1.066×Lunar Prodigy ALM [kg]–2.064, R²=0.952).
Conclusion
Although measurements of body composition including muscle mass by the two DXA systems correlated strongly, significant differences were observed. Calibration equations should enable mutual conversion between different DXA systems.

Citations

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Total and regional appendicular skeletal muscle mass prediction from dual-energy X-ray absorptiometry body composition models
Cassidy McCarthy, Grant M. Tinsley, Anja Bosy-Westphal, Manfred J. Müller, John Shepherd, Dympna Gallagher, Steven B. Heymsfield
Scientific Reports.2023;[Epub] CrossRef
Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa
Mícheál Ó Breasail, Ramatoulie Janha, Ayse Zengin, Camille Pearse, Landing Jarjou, Ann Prentice, Kate A. Ward
Calcified Tissue International.2023; 112(5): 573. CrossRef
Estimation of Absolute and Relative Body Fat Content Using Noninvasive Surrogates: Can DXA Be Bypassed?
David J. Greenblatt, Christopher D. Bruno, Jerold S. Harmatz, Bess Dawson‐Hughes, Qingchen Zhang, Chunhui Li, Christina R. Chow
The Journal of Clinical Pharmacology.2023;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Musclin Is Related to Insulin Resistance and Body Composition, but Not to Body Mass Index or Cardiorespiratory Capacity in Adults: Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis Valbuena, Andrés F. Milán, María C. Trillos-Almanza, Sergio Granados, Miguel Peña, Mauricio Estrada-Castrillón, Juan C. Aristizábal, Raúl Narvez-Sanchez, Jaime Gallo-Villegas, Juan C. Calderón; Endocrinol Metab. 2021;36(5):1055-1068. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1104

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Background
We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.
Methods
A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.
Results
The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VO_peak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m² vs. 27.4± 3.6 kg/m²), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VO_peak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.
Conclusion
In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

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Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation
Wonjun Cho, Heeseung Oh, Sung Woo Choi, A. M. Abd El-Aty, Fatma Yeşilyurt, Ji Hoon Jeong, Tae Woo Jung
Inflammation.2024; 47(1): 1. CrossRef
Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2
Kaiyi Zhang, Ning Xie, Huaqiong Ye, Jiakun Miao, Boce Xia, Yu Yang, Huanqi Peng, Shuang Xu, Tianwen Wu, Cong Tao, Jinxue Ruan, Yanfang Wang, Shulin Yang
iScience.2024; 27(1): 108590. CrossRef
Myokines: metabolic regulation in obesity and type 2 diabetes
Zhi-Tian Chen, Zhi-Xuan Weng, Jiandie D Lin, Zhuo-Xian Meng
Life Metabolism.2024;[Epub] 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
European Journal of Applied Physiology.2023; 123(5): 945. CrossRef
Serum Levels of Myonectin Are Lower in Adults with Metabolic Syndrome and Are Negatively Correlated with Android Fat Mass
Jorge L. Petro, María Carolina Fragozo-Ramos, Andrés F. Milán, Juan C. Aristizabal, Jaime A. Gallo-Villegas, Juan C. Calderón
International Journal of Molecular Sciences.2023; 24(8): 6874. CrossRef
The correlation of serum musclin with diabetic nephropathy
Jie Zhang, Jing Shi, Zengguang Cheng, Wenchao Hu
Cytokine.2023; 167: 156211. CrossRef
Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial
Jaime Gallo-Villegas, Leonardo A. Castro-Valencia, Laura Pérez, Daniel Restrepo, Oscar Guerrero, Sergio Cardona, Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis H. Valbuena, Miguel Peña, Andrés F. Milán, Maria C. Trillos-Almanza, Sergio Granados, Juan C.
European Journal of Applied Physiology.2022; 122(2): 331. CrossRef
Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle
Paola Llanos, Jesus Palomero
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Diabetes, Obesity and Metabolism
Differences in Abdominal Body Composition According to Glycemic Status: An Inverse Probability Treatment Weighting Analysis: Seungbong Han, Young-Jee Jeon, Gyung-Min Park, Tae Young Lee, Soon Eun Park, Gyeongseok Yu, Byung Ju Kang; Endocrinol Metab. 2021;36(4):855-864. Published online August 11, 2021; DOI: https://doi.org/10.3803/EnM.2021.1086

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Background
Several studies have reported that abdominal fat and muscle changes occur in diabetic patients. However, there are few studies about such changes among prediabetic patients. In this study, we evaluated the differences in abdominal fat and muscles based on abdominopelvic computed tomography in prediabetic and diabetic subjects compared to normal subjects.
Methods
We performed a cross-sectional study using health examination data from March 2014 to June 2019 at Ulsan University Hospital and classified subjects into normal, prediabetic, and diabetic groups. We analyzed the body mass index corrected area of intra-abdominal components among the three groups using inverse probability treatment weighting (IPTW) analysis.
Results
Overall, 8,030 subjects were enrolled; 5,137 (64.0%), 2,364 (29.4%), and 529 (6.6%) subjects were included in the normal, prediabetic, and diabetic groups, respectively. After IPTW adjustment of baseline characteristics, there were significant differences in log visceral adipose tissue index (VATI; 1.22±0.64 cm²/[kg/m²] vs. 1.30±0.63 cm²/[kg/m²] vs. 1.47±0.64 cm²/[kg/m²], P<0.001) and low-attenuation muscle index (LAMI; 1.02±0.36 cm²/[kg/m²] vs. 1.03±0.36 cm²/[kg/m²] vs. 1.09±0.36 cm²/[kg/m²], P<0.001) among the normal, prediabetic, and diabetic groups. Prediabetic subjects had higher log VATI (estimated coefficient= 0.082, P<0.001), and diabetic subjects had higher log VATI (estimated coefficient=0.248, P<0.001) and LAMI (estimated coefficient=0.078, P<0.001) compared to normal subjects.
Conclusion
Considering that VATI and LAMI represented visceral fat and lipid-rich skeletal muscle volumes, respectively, visceral obesity was identified in both prediabetic and diabetic subjects compared to normal subjects in this study. However, intra-muscular fat infiltration was observed in diabetic subjects only.

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Testosterone is associated with abdominal body composition derived from computed tomography: a large cross sectional study
Seungbong Han, Young-Jee Jeon, Tae Young Lee, Gyung-Min Park, Sungchan Park, Seong Cheol Kim
Scientific Reports.2022;[Epub] CrossRef

Review Article

Diabetes, Obesity and Metabolism
Exercise/Resistance Training and Muscle Stem Cells: So-ichiro Fukada, Ayasa Nakamura; Endocrinol Metab. 2021;36(4):737-744. Published online August 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.401

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Skeletal muscle has attracted attention as endocrine organ, because exercise-dependent cytokines called myokines/exerkines are released from skeletal muscle and are involved in systemic functions. While, local mechanical loading to skeletal muscle by exercise or resistance training alters myofiber type and size and myonuclear number. Skeletal muscle-resident stem cells, known as muscle satellite cells (MuSCs), are responsible for the increased number of myonuclei. Under steady conditions, MuSCs are maintained in a mitotically quiescent state but exit from that state and start to proliferate in response to high physical activity. Alterations in MuSC behavior occur when myofibers are damaged, but the lethal damage to myofibers does not seem to evoke mechanical loading-dependent MuSC activation and proliferation. Given that MuSCs proliferate without damage, it is unclear how the different behaviors of MuSCs are controlled by different physical activities. Recent studies demonstrated that myonuclear number reflects the size of myofibers; hence, it is crucial to know the properties of MuSCs and the mechanism of myonuclear accretion by MuSCs. In addition, the elucidation of mechanical load-dependent changes in muscle resident cells, including MuSCs, will be necessary for the discovery of new myokines/exerkines and understating skeletal muscle diseases.

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Control of muscle satellite cell function by specific exercise‐induced cytokines and their applications in muscle maintenance
Qian Guo, Qing Luo, Guanbin Song
Journal of Cachexia, Sarcopenia and Muscle.2024; 15(2): 466. CrossRef
Resistance exercise preconditioning prevents disuse muscle atrophy by inhibiting apoptosis and protein degradation via SESN2 in C57BL/6J mice
Yating Huang, Chenxin Jiang, Xiuru Li, Sujuan Liu, Yanmei Niu, Li Fu
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(4): 167111. CrossRef
Anthropometric, muscle and serum myokine levels effects of physical exercise with an online platform in female patients with obesity
David Primo, Olatz Izaola, Juan Jose Lopez Gomez, Daniel de Luis
Endocrinología, Diabetes y Nutrición.2023; 70(7): 484. CrossRef
Anthropometric, muscle and serum myokine levels effects of physical exercise with an online platform in female patients with obesity
David Primo, Olatz Izaola, Juan Jose Lopez Gomez, Daniel de Luis
Endocrinología, Diabetes y Nutrición (English ed.).2023; 70(7): 484. CrossRef
The muscle stem cell niche at a glance
Margaret Hung, Hsiao-Fan Lo, Grace E. L. Jones, Robert S. Krauss
Journal of Cell Science.2023;[Epub] CrossRef
Exercise Therapy for People With Sarcopenic Obesity: Myokines and Adipokines as Effective Actors
Hamed Alizadeh Pahlavani
Frontiers in Endocrinology.2022;[Epub] CrossRef
Molecular mechanisms of exercise contributing to tissue regeneration
Jibao Chen, Ren Zhou, Ye Feng, Lin Cheng
Signal Transduction and Targeted Therapy.2022;[Epub] CrossRef

Original Article

Adrenal Gland
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor: Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(4):865-874. Published online July 30, 2021; DOI: https://doi.org/10.3803/EnM.2021.1108

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Background
Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research.
Results
Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone.
Conclusion
These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

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Jorge E. Aedo, Rodrigo Zuloaga, Daniela Aravena-Canales, Alfredo Molina, Juan Antonio Valdés
Frontiers in Physiology.2023;[Epub] CrossRef
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Yi Wang, Chuan Xiang Li, Ying Ni Lin, Li Yue Zhang, Shi Qi Li, Liu Zhang, Ya Ru Yan, Fang Ying Lu, Ning Li, Qing Yun Li
Frontiers in Endocrinology.2022;[Epub] CrossRef
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Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
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Review Article

Diabetes, Obesity and Metabolism
Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics: Jong Hyeon Yoon, Ki-Sun Kwon; Endocrinol Metab. 2021;36(3):478-490. Published online June 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1081

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Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

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