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36 "Aging"
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Original Articles
Carnitine Metabolite as a Potential Circulating Biomarker for Sarcopenia in Men
Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young‑Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee
Received July 28, 2024  Accepted October 7, 2024  Published online November 28, 2024  
DOI: https://doi.org/10.3803/EnM.2024.2117    [Epub ahead of print]
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  • 31 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Methods
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
Results
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
Conclusion
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.
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Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health
Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim
Received July 17, 2024  Accepted August 7, 2024  Published online October 24, 2024  
DOI: https://doi.org/10.3803/EnM.2024.2100    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods
We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results
After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion
These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.
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Miscellaneous
Differences in Type 2 Fiber Composition in the Vastus Lateralis and Gluteus Maximus of Patients with Hip Fractures
Jingwen Tian, Minchul Song, Kyu Jeong Cho, Ho Yeop Lee, Sang Hyeon Ju, Jung Ryul Lim, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Jung-Mo Hwang, Hyon-Seung Yi
Endocrinol Metab. 2024;39(3):521-530.   Published online June 11, 2024
DOI: https://doi.org/10.3803/EnM.2024.1935
  • 2,238 View
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  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls.
Methods
A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type.
Results
In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters.
Conclusion
This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.

Citations

Citations to this article as recorded by  
  • Volume and quality of the gluteal muscles are associated with early physical function after total hip arthroplasty
    Makoto Iwasa, Keisuke Uemura, Mazen Soufi, Yoshito Otake, Tomofumi Kinoshita, Tatsuhiko Kutsuna, Kazuma Takashima, Hidetoshi Hamada, Yoshinobu Sato, Nobuhiko Sugano, Seiji Okada, Masaki Takao
    International Journal of Computer Assisted Radiology and Surgery.2025;[Epub]     CrossRef
  • Tourniquet Use During ACL Reconstruction Is Associated With Postoperative Quadriceps Atrophy and Pain but No Negative Effects in the Long Term: A Systematic Review
    Caleb V. Hayes, Saad M. Ibrahim, Anna E. Crawford, James R. Jones, Mathew D. Hargreaves, Clay A. Rahaman, Eugene W. Brabston, Thomas B. Evely, Aaron J. Casp, Kevin E. Wilk, Amit M. Momaya
    Arthroscopy, Sports Medicine, and Rehabilitation.2024; : 101040.     CrossRef
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Review Articles
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
  • 4,642 View
  • 143 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Editorial: Tumor metabolism and programmed cell death
    Dan-Lan Pu, Qi-Nan Wu
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
    Han Wang, Yang Liu, Aifa Tang, Xiansheng Zhang
    European Journal of Medical Research.2024;[Epub]     CrossRef
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Calcium & bone metabolism
Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis
Brendan F. Boyce, Jinbo Li, Zhenqiang Yao, Lianping Xing
Endocrinol Metab. 2023;38(5):504-521.   Published online September 26, 2023
DOI: https://doi.org/10.3803/EnM.2023.501
  • 4,994 View
  • 167 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.

Citations

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  • The Role of Rosavin in the Pathophysiology of Bone Metabolism
    Piotr Wojdasiewicz, Paweł Turczyn, Anna Lach-Gruba, Łukasz A. Poniatowski, Daryush Purrahman, Mohammad-Reza Mahmoudian-Sani, Dariusz Szukiewicz
    International Journal of Molecular Sciences.2024; 25(4): 2117.     CrossRef
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    Hao Luo, Linfeng Li, Song Han, Tao Liu
    International Journal of Immunogenetics.2024; 51(3): 130.     CrossRef
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    Chun-Yi Huang, Huynh Hoai Thuong Le, Hsiao-Chi Tsai, Chih-Hsin Tang, Jian-Hong Yu
    Journal of Dental Sciences.2024; 19(3): 1452.     CrossRef
  • Anti-arthritic and immunomodulatory efficacy of Micromeria biflora Benth extract and its fractions in rats by restoring oxidative stress, metalloproteinases, pro-inflammatory and anti-inflammatory cytokines network
    Fakhria A. Al-Joufi, Ambreen Malik Uttra, Sumera Qasim, Urooj Iqbal, Nabeela Tabassum Sial, Noura M. Alhumaid
    Inflammopharmacology.2024; 32(4): 2477.     CrossRef
  • Evaluation of Immunohistochemical Biomarkers in Diabetic Wistar Rats with Periodontal Disease
    Ioana Scrobota, Ioan Andrei Tig, Andrea Olivia Marcu, Georgiana Ioana Potra Cicalau, Liliana Sachelarie, Gilda Iova
    Journal of Personalized Medicine.2024; 14(5): 527.     CrossRef
  • The role of magnesium in the pathogenesis of osteoporosis
    Lin Liu, Pan Luo, Pengfei Wen, Peng Xu
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Current Perspectives of Protein in Bone Tissue Engineering: Bone Structure, Ideal Scaffolds, Fabrication Techniques, Applications, Scopes, and Future Advances
    Muhammad Umar Aslam Khan, Muhammad Azhar Aslam, Mohd Faizal Bin Abdullah, Goran M. Stojanović
    ACS Applied Bio Materials.2024; 7(8): 5082.     CrossRef
  • Effect of recombinant human bone morphogenetic protein-2 and osteoprotegerin-Fc in MC3T3-E1 cells: beyond challenges to success
    Chang Hoon Lee
    Journal of Rheumatic Diseases.2024; 31(3): 133.     CrossRef
  • Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells
    Yerin Yu, Somin Lee, Minsung Bock, Seong Bae An, Hae Eun Shin, Jong Seop Rim, Jun-oh Kwon, Kwang-Sook Park, Inbo Han
    International Journal of Molecular Sciences.2024; 25(15): 8174.     CrossRef
  • Identification of novel RANKL inhibitors through in silico analysis
    Yingying Jiang, Xiaogang Luo, Zhanpeng Zheng, Shun Wen, Hongwei Gao, Cheng Xu, Min Jiang, Siyuan Wang
    Bioorganic Chemistry.2024; 153: 107826.     CrossRef
  • Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions
    Valentina Granata, Dario Strina, Maria Lucia Schiavone, Barbara Bottazzi, Alberto Mantovani, Antonio Inforzato, Cristina Sobacchi
    International Journal of Molecular Sciences.2023; 24(23): 16648.     CrossRef
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Calcium & bone metabolism
Skeletal Senescence with Aging and Type 2 Diabetes
Joshua Nicholas Farr
Endocrinol Metab. 2023;38(3):295-301.   Published online June 14, 2023
DOI: https://doi.org/10.3803/EnM.2023.1727
  • 4,537 View
  • 141 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDFPubReader   ePub   
Osteoporosis and type 2 diabetes (T2D) are common diseases that often coexist. While both of these diseases are associated with poor bone quality and increased fracture risk, their pathogenesis of increased fracture risk differs and is multifactorial. Mounting evidence now indicates that key fundamental mechanisms that are central to both aging and energy metabolism exist. Importantly, these mechanisms represent potentially modifiable therapeutic targets for interventions that could prevent or alleviate multiple complications of osteoporosis and T2D, including poor bone quality. One such mechanism that has gained increasing momentum is senescence, which is a cell fate that contributes to multiple chronic diseases. Accumulating evidence has established that numerous boneresident cell types become susceptible to cellular senescence with old age. Recent work also demonstrates that T2D causes the premature accumulation of senescent osteocytes during young adulthood, at least in mice, although it remains to be seen which other bone-resident cell types become senescent with T2D. Given that therapeutically removing senescent cells can alleviate age-related bone loss and T2D-induced metabolic dysfunction, it will be important in future studies to rigorously test whether interventions that eliminate senescent cells can also alleviate skeletal dysfunction in context of T2D, as it does with aging.

Citations

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    Weihua Li, Siyu Xie, Shengdong Zhong, Liting Lan
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
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    Shizhen Lei, Mang Hu, Zhongtao Wei
    Frontiers in Aging Neuroscience.2024;[Epub]     CrossRef
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    Ying Liu, Jiao Chen
    Frontiers in Aging Neuroscience.2024;[Epub]     CrossRef
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Miscellaneous
Brown Adipose Tissue: Activation and Metabolism in Humans
Imane Hachemi, Mueez U-Din
Endocrinol Metab. 2023;38(2):214-222.   Published online March 27, 2023
DOI: https://doi.org/10.3803/EnM.2023.1659
  • 17,545 View
  • 733 Download
  • 9 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Brown adipose tissue (BAT) is a thermogenic organ contributing to non-shivering thermogenesis. BAT becomes active under cold stress via sympathetic nervous system activation. However, recent evidence has suggested that BAT may also be active at thermoneutrality and in a postprandial state. BAT has superior energy dissipation capacity compared to white adipose tissue (WAT) and muscles. Thus, it has been proposed that the recruitment and activation of additional BAT may increase the overall energy-expending capacity in humans, potentially improving current whole-body weight management strategies. Nutrition plays a central role in obesity and weight management. Thus, this review discusses human studies describing BAT hyper-metabolism after dietary interventions. Nutritional agents that can potentially recruit brown adipocytes via the process of BAT-WAT transdifferentiation are also discussed.

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    CardioMetabolic Syndrome Journal.2024; 4(2): 57.     CrossRef
  • The Interplay between Liver and Adipose Tissue in the Onset of Liver Diseases: Exploring the Role of Vitamin Deficiency
    Ivan Tattoli, Aimee Rachel Mathew, Antonella Verrienti, Lucia Pallotta, Carola Severi, Fausto Andreola, Virve Cavallucci, Mauro Giorgi, Mara Massimi, Lapo Bencini, Marco Fidaleo
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Calcium & Bone Metabolism
Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism
Hye-Sun Park, Namki Hong, Jong Ju Jeong, Mijin Yun, Yumie Rhee
Endocrinol Metab. 2022;37(5):744-755.   Published online October 25, 2022
DOI: https://doi.org/10.3803/EnM.2022.1589
  • 6,623 View
  • 470 Download
  • 11 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

Citations

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  • Diagnostic Ability and Correlation of Digital 11C-Methionine PET/CT in Primary Hyperparathyroidism with Inconclusive Standard Imaging
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    Piyush Aggarwal, Vinisha Gunasekaran, Ashwani Sood, Bhagwant Rai Mittal
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  • A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion
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  • Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue
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  • Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review
    Max H. M. C. Scheepers, Zaid Al-Difaie, Lloyd Brandts, Andrea Peeters, Bjorn Winkens, Mahdi Al-Taher, Sanne M. E. Engelen, Tim Lubbers, Bas Havekes, Nicole D. Bouvy, Alida A. Postma
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Original Articles
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
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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  • Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
    Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
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Diabetes, Obesity and Metabolism
The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018
Ji Cheol Bae, Lauren A. Beste, Kristina M. Utzschneider
Endocrinol Metab. 2022;37(3):455-465.   Published online June 21, 2022
DOI: https://doi.org/10.3803/EnM.2022.1434
  • 5,988 View
  • 154 Download
  • 15 Web of Science
  • 15 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods
We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results
Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion
Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

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Review Article
Thyroid
Thyroid Function across the Lifespan: Do Age-Related Changes Matter?
John P. Walsh
Endocrinol Metab. 2022;37(2):208-219.   Published online April 14, 2022
DOI: https://doi.org/10.3803/EnM.2022.1463
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  • 18 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   ePub   
Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.

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Original Articles
Calcium & Bone Metabolism
Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults
Yeon Woo Jung, Namki Hong, Joon Chae Na, Woong Kyu Han, Yumie Rhee
Endocrinol Metab. 2021;36(6):1201-1210.   Published online December 13, 2021
DOI: https://doi.org/10.3803/EnM.2021.1206
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
A decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.
Methods
In a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.
Results
L3SMD showed constant decline from the second decade (annual change –0.38% and –0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (–0.37% and –0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).
Conclusion
L3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.

Citations

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  • Changes in thoracic radio density after living donor liver transplantation
    Atsushi Miki, Yasunaru Sakuma, Yukihiro Sanada, Jun Watanabe, Yasuharu Onishi, Noriki Okada, Toshio Horiuchi, Takahiko Omameuda, Takumi Teratani, Alan K. Lefor, Joji Kitayama, Naohiro Sata
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Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules
Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho
Endocrinol Metab. 2021;36(5):1111-1120.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1208
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  • 9 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

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Close layer
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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  • 388 Download
  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   ePub   
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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Original Article
Endocrine Research
Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults
Da Ae Kim, So Jeong Park, Jin Young Lee, Jeoung Hee Kim, Seungjoo Lee, Eunju Lee, Il-Young Jang, Hee-Won Jung, Jin Hoon Park, Beom-Jun Kim
Endocrinol Metab. 2021;36(2):455-465.   Published online April 14, 2021
DOI: https://doi.org/10.3803/EnM.2020.942
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline.
Results
Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index.
Conclusion
Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

Citations

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