Endocrinology and Metabolism

Review Articles

Hypothalamus and Pituitary Gland
Independent Skeletal Actions of Pituitary Hormones: Se-Min Kim, Farhath Sultana, Funda Korkmaz, Daria Lizneva, Tony Yuen, Mone Zaidi; Endocrinol Metab. 2022;37(5):719-731. Published online September 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1573

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Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells—osteoblasts and osteoclasts—express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

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New tools for bone health assessment in secreting pituitary adenomas
Meliha Melin Uygur, Stefano Frara, Luigi di Filippo, Andrea Giustina
Trends in Endocrinology & Metabolism.2023; 34(4): 231. CrossRef
A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
Dongjin Lee, Moon Ahn
Metabolites.2023; 13(3): 372. CrossRef
The mechanism of oxytocin and its receptors in regulating cells in bone metabolism
Liu Feixiang, Feng Yanchen, Li Xiang, Zhang Yunke, Miao Jinxin, Wang Jianru, Lin Zixuan
Frontiers in Pharmacology.2023;[Epub] CrossRef
To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques
Weisen Fan, Yan Meng, Jing Zhang, Muzhen Li, Yingjie Zhang, Xintian Qu, Xin Xiu
Scientific Reports.2023;[Epub] CrossRef

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

Original Article

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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The role of the mitochondrial trans-sulfuration in cerebro-cardio renal dysfunction during trisomy down syndrome
Sathnur Pushpakumar, Mahavir Singh, Utpal Sen, N. Tyagi, Suresh C. Tyagi
Molecular and Cellular Biochemistry.2024; 479(4): 825. CrossRef
Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018
Sha Yang, Zhenyu Dong, Jiaqi Zhao, Lijia Yuan, Yao Xiao, Xing Luo, Zhuyang Zhao, Xia Kang, Kanglai Tang, Ming Chen, Liu Feng
Frontiers in Nutrition.2024;[Epub] CrossRef
Association of Triglyceride-Glucose Index with the Risk of Hyperhomocysteinemia Among Chinese Male Bus Drivers: A Longitudinal Study
Juan Xiong, Yanxia Wu, Lingling Huang, Xujuan Zheng
International Journal of General Medicine.2023; Volume 16: 2857. CrossRef
Relationship between hyperhomocysteinemia and coexisting obesity with low skeletal muscle mass in asymptomatic adult population
Tae Kyung Yoo, Hye Chang Rhim, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park
Scientific Reports.2022;[Epub] CrossRef
Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study
Hongwei Yu, Gan Luo, Tianwei Sun, Qiong Tang
Frontiers in Genetics.2022;[Epub] CrossRef
Association between serum homocysteine and sarcopenia among hospitalized older Chinese adults: a cross-sectional study
Bing Lu, Lingyu Shen, Haiqiong Zhu, Ling Xi, Wei Wang, Xiaojun Ouyang
BMC Geriatrics.2022;[Epub] CrossRef

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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A CT-based Deep Learning Model for Predicting Subsequent Fracture Risk in Patients with Hip Fracture
Yisak Kim, Young-Gon Kim, Jung-Wee Park, Byung Woo Kim, Youmin Shin, Sung Hye Kong, Jung Hee Kim, Young-Kyun Lee, Sang Wan Kim, Chan Soo Shin
Radiology.2024;[Epub] CrossRef
Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation
Jie Chen, Yue Li, Chengjie Li, Turun Song
Abdominal Radiology.2024; 49(4): 1210. CrossRef
Fatty infiltration of gastrocnemius–soleus muscle complex: Considerations for myosteatosis rehabilitation
Catherine Hatzantonis, Lalith Satkunam, Karyne N. Rabey, Jennifer C. Hocking, Anne M. R. Agur
Journal of Anatomy.2024;[Epub] CrossRef
Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity
Cheng-Le Zhuang, Hao-Fan Wu, Hao-Jie Jiang, Feng-Min Zhang, Han-Ping Shi, Zhen Yu, Xian Shen, Xiao-Lei Chen, Su-Lin Wang
Nutrition.2024; 122: 112391. CrossRef
Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes
Fu-Peng Liu, Mu-Jie Guo, Qing Yang, Yan-Ying Li, Yan-Gang Wang, Mei Zhang
World Journal of Diabetes.2024; 15(3): 429. CrossRef
Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction‐associated steatotic liver disease?
Guillaume Henin, Audrey Loumaye, Louise Deldicque, Isabelle A. Leclercq, Nicolas Lanthier
Liver International.2024;[Epub] CrossRef
Association of serum gamma-glutamyl transferase with myosteatosis assessed by muscle quality mapping using abdominal computed tomography
Han Na Jung, Yun Kyung Cho, Hwi Seung Kim, Eun Hee Kim, Min Jung Lee, Joong-Yeol Park, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
Clinical Imaging.2023; 93: 4. CrossRef
Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross‐sectional study
Shi Zhang, Yaping Huang, Jing Li, Xincheng Wang, Xiaohe Wang, Minying Zhang, Yanju Zhang, Meiyang Du, Jingna Lin, Chunjun Li
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
Association between hypertension and myosteatosis evaluated by abdominal computed tomography
Han Na Jung, Yun Kyung Cho, Hwi Seung Kim, Eun Hee Kim, Min Jung Lee, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
Hypertension Research.2023; 46(4): 845. 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
Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia
Carla Maria Avesani, Aline Miroski de Abreu, Heitor S. Ribeiro, Torkel B. Brismar, Peter Stenvinkel, Alice Sabatino, Bengt Lindholm
Journal of Nephrology.2023; 36(3): 895. CrossRef
IDF2022-1139 Association Between Dyslipidemia And Myosteatosis Using Visual Muscular Quality Map In Computed Tomography
H.S. Kim, H.N. Jung, Y.K. Cho, E.H. Kim, M.J. Lee, W.J. Lee, J.Y. Park, H.K. Kim, C.H. Jung
Diabetes Research and Clinical Practice.2023; 197: 110467. CrossRef
The role of skeletal muscle mass on cardiovascular disease risk: an emerging role on modulating lipid profile
Evangelia Damigou, Matina Kouvari, Demosthenes Panagiotakos
Current Opinion in Cardiology.2023; 38(4): 352. CrossRef
Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors
Lisa B. Westenberg, Marcel Zorgdrager, Tim D. A. Swaab, Marco van Londen, Stephan J. L. Bakker, Henri G. D. Leuvenink, Alain R. Viddeleer, Robert A. Pol
Scientific Reports.2023;[Epub] CrossRef
Association between sarcopenic obesity and poor muscle quality based on muscle quality map and abdominal computed tomography
Yun Kyung Cho, Han Na Jung, Eun Hee Kim, Min Jung Lee, Joong‐Yeol Park, Woo Je Lee, Hong‐Kyu Kim, Chang Hee Jung
Obesity.2023; 31(6): 1547. CrossRef
Increase in skeletal muscular adiposity and cognitive decline in a biracial cohort of older men and women
Caterina Rosano, Anne Newman, Adam Santanasto, Xiaonan Zhu, Bret Goodpaster, Iva Miljkovic
Journal of the American Geriatrics Society.2023; 71(9): 2759. CrossRef
Evaluation of Paraspinal Muscle Degeneration on Pain Relief after Percutaneous Epidural Adhesiolysis in Patients with Degenerative Lumbar Spinal Disease
Misun Kang, Shin Hyung Kim, Minju Jo, Hyun Eom Jung, Jungbin Bae, Hee Jung Kim
Medicina.2023; 59(6): 1118. CrossRef
Sarcopenic obesity and its relation with muscle quality and mortality in patients on chronic hemodialysis
Alice Sabatino, Carla Maria Avesani, Giuseppe Regolisti, Marianna Adinolfi, Giuseppe Benigno, Marco Delsante, Enrico Fiaccadori, Ilaria Gandolfini
Clinical Nutrition.2023; 42(8): 1359. CrossRef
Association between computed tomography‐assessed sarcopenia and mortality in patients with anti‐neutrophil cytoplasmic antibody‐associated vasculitis
Sung Soo Ahn, Yong‐Beom Park, Sang‐Won Lee
International Journal of Rheumatic Diseases.2023; 26(9): 1704. CrossRef
Association Between Insulin Resistance and Myosteatosis Measured by Abdominal Computed Tomography
Myung Jin Kim, Yun Kyung Cho, Han Na Jung, Eun Hee Kim, Min Jung Lee, Chang Hee Jung, Joong-Yeol Park, Hong-Kyu Kim, Woo Je Lee
The Journal of Clinical Endocrinology & Metabolism.2023; 108(12): 3100. CrossRef
Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
Clinical and Molecular Hepatology.2023; 29(4): 987. CrossRef
Different computed tomography parameters for defining myosteatosis in patients with advanced non-small cell lung cancer
Wenyi Zhang, Jing Tang, Huiyu Tang, Lingling Xie, Jing Wang, Jinhui Wu, Ming Yang
Clinical Nutrition.2023; 42(12): 2414. CrossRef
All you need to know about sarcopenia: a short guide for an internal medicine physician in questions and answers
G. R. Bikbavova, M. A. Livzan, D. V. Tikhonravova
Bulletin of Siberian Medicine.2023; 22(3): 88. CrossRef
Muscle Fat Content Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Chinese Adults
W. Guo, X. Zhao, D. Cheng, X. Liang, M. Miao, X. Li, J. Lu, N. Xu, Shuang Hu, Qun Zhang
The Journal of nutrition, health and aging.2023; 27(11): 960. CrossRef
Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria
Luis M. Luengo-Pérez, Mercedes Fernández-Bueso, Ana Ambrojo, Marta Guijarro, Ana Cristina Ferreira, Luís Pereira-da-Silva, André Moreira-Rosário, Ana Faria, Conceição Calhau, Anne Daly, Anita MacDonald, Júlio César Rocha
Nutrients.2023; 15(24): 5133. CrossRef
Assessment of Muscle Quantity, Quality and Function
Bo Kyung Koo
Journal of Obesity & Metabolic Syndrome.2022; 31(1): 9. CrossRef
Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients
Hee Jung Kim, Miribi Rho, Kyung Bong Yoon, Minju Jo, Dong Woo Lee, Shin Hyung Kim
Pain Practice.2022; 22(7): 621. CrossRef
Sarcopenia, Obesity, Sarcopenic Obesity and Risk of Poor Nutritional Status in Polish Community-Dwelling Older People Aged 60 Years and Over
Marika Murawiak, Roma Krzymińska-Siemaszko, Aleksandra Kaluźniak-Szymanowska, Marta Lewandowicz, Sławomir Tobis, Katarzyna Wieczorowska-Tobis, Ewa Deskur-Śmielecka
Nutrients.2022; 14(14): 2889. CrossRef
Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation
Amedeo Lonardo, Alessandro Mantovani, Salvatore Petta, Amedeo Carraro, Christopher D. Byrne, Giovanni Targher
Nature Reviews Endocrinology.2022; 18(10): 638. CrossRef

Original Article

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
Cells.2022; 11(24): 4008. CrossRef

Review Articles

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.

Citations

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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

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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Saniya Khan, Sunil Kumar, Sourya Acharya, Anil Wanjari
Journal of Health and Allied Sciences NU.2023; 13(04): 453. CrossRef
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Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob van Maanen, Roger A Fielding, Lewis A Lipsitz
The Journals of Gerontology: Series A.2023; 78(Supplement): 44. CrossRef
Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy
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Biochemical and Biophysical Research Communications.2022; 586: 157. CrossRef
Adeno-associated virus-mediated expression of an inactive CaMKIIβ mutant enhances muscle mass and strength in mice
Takahiro Eguchi, Yuji Yamanashi
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Original Article

Diabetes, Obesity and Metabolism
Reference Values for Skeletal Muscle Mass at the Third Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population: Ja Kyung Yoon, Sunyoung Lee, Kyoung Won Kim, Ji Eun Lee, Jeong Ah Hwang, Taeyong Park, Jeongjin Lee; Endocrinol Metab. 2021;36(3):672-677. Published online June 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.1041

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Background
Sarcopenia is defined as the loss of skeletal muscle mass and is associated with negative clinical outcomes. This study aimed to establish sex-specific cutoff values for the skeletal muscle area (SMA) and skeletal muscle index (SMI) at the third lumbar vertebral (L3) level using computed tomography (CT) imaging to identify sarcopenia in healthy Korean liver donors.
Methods
This retrospective study included 659 healthy liver donors (408 men and 251 women) aged 20 to 60 years who had undergone abdominal CT examinations between January 2017 and December 2018. Assessment of body composition was performed with an automated segmentation technique using a deep-learning system. Sex-specific SMA and SMI distributions were assessed, and cutoff values for determining sarcopenia were defined as values at either two standard deviations (SDs) below the mean reference value or below the fifth percentile.
Results
Using the SD definition, cutoff values for SMA and SMI were 117.04 cm² and 39.33 cm²/m², respectively, in men and 71.39 cm² and 27.77 cm²/m², respectively, in women. Using the fifth percentile definition, cutoff values for SMA and SMI were 126.88 cm² and 40.96 cm²/m², respectively, in men and 78.85 cm² and 30.60 cm²/m², respectively, in women.
Conclusion
Our data provide sex-specific cutoff values for the SMA and SMI at the L3 level measured by CT imaging in a healthy Korean population, which may be applicable for identifying sarcopenia in this population.

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Review Article

Miscellaneous
Sarcopenia and Muscle Aging: A Brief Overview: Tam Dao, Alexander E. Green, Yun A Kim, Sung-Jin Bae, Ki-Tae Ha, Karim Gariani, Mi-ra Lee, Keir J. Menzies, Dongryeol Ryu; Endocrinol Metab. 2020;35(4):716-732. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.405

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The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD⁺) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

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Namgok Lecture 2019

Obesity and Metabolism
Impact of Skeletal Muscle Mass on Metabolic Health: Gyuri Kim, Jae Hyeon Kim; Endocrinol Metab. 2020;35(1):1-6. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.1

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Abstract PDF PubReader ePub

Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.

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Review Article

Obesity and Metabolism
Connecting Myokines and Metabolism: Rexford S. Ahima, Hyeong-Kyu Park; Endocrinol Metab. 2015;30(3):235-245. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.235

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134 Download
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Abstract PDF PubReader

Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

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Original Article

Thyroid
Expression of Thyroid Stimulating Hormone Receptor mRNA in Mouse C2C12 Skeletal Muscle Cells: Jung Hun Ohn, Sun Kyoung Han, Do Joon Park, Kyong Soo Park, Young Joo Park; Endocrinol Metab. 2013;28(2):119-124. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.119

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Abstract PDF PubReader

Background

We analyzed whether thyroid stimulating hormone receptor (TSH-R) is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types.

Methods

TSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR) in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH.

Results

TSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes.

Conclusion

TSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.

Citations

Citations to this article as recorded by

Associations between thyroid hormones and appendicular skeletal muscle index, and hand grip strength in people with diabetes: The KAMOGAWA-A study
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Diabetes Research and Clinical Practice.2024; 209: 111573. CrossRef
Clinical parameters correlated with the psoas muscle index in Japanese individuals with type 2 diabetes mellitus
Emi Asano-Hayami, Yoshiaki Morishita, Tomohide Hayami, Yuka Shibata, Toshiki Kiyose, Sachiko Sasajima, Yusuke Hayashi, Mikio Motegi, Makoto Kato, Saeko Asano, Hiromi Nakai-Shimoda, Yuichiro Yamada, Emiri Miura-Yura, Tatsuhito Himeno, Masaki Kondo, Shin Ts
Diabetology International.2023; 14(1): 76. CrossRef
Effect of Thyroid-Stimulating Hormone Suppression on Muscle Function After Total Thyroidectomy in Patients With Thyroid Cancer
Jun Choul Lee, Byong-Sop Song, Young Mi Kang, Yu-Ri Kim, Yea Eun Kang, Ju Hee Lee, Minho Shong, Hyon-Seung Yi
Frontiers in Endocrinology.2021;[Epub] CrossRef
Different Relationships Between Thyrotropin and Muscle Strength According to Sex and Age in Euthyroid Koreans (The 6th Korea National Health and Nutritional Examination Survey 2014–2015)
Seong Hee Ahn, Da Hea Seo, Yongin Cho, Mihye Jung, So Hun Kim, Seongbin Hong
Thyroid.2020; 30(12): 1710. CrossRef
A Significant Association of Upper Limb Muscle Strength with Thyroid Function in Overweight and Obese Population: A Study of the Sixth Korea National Health and Nutrition Examination Survey (KNHANES 2014-2015)
Jeongmin Lee, Kwanhoon Jo, Jeonghoon Ha, Dong-Jun Lim, Jung Min Lee, Sang-Ah Chang, Moo Il Kang, Min-Hee Kim, Flavia Magri
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Hui Tang, Shuai Deng, Jian-guang Cai, Xue-nan Ma, Man Liu, Liang Zhou
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Thyroid Function as a Predictor of Handgrip Strength Among Middle-Aged and Older Euthyroid Adults: The TCLSIH Cohort Study
Yeqing Gu, Ge Meng, Hongmei Wu, Qing Zhang, Li Liu, Xue Bao, Yawen Wang, Shunming Zhang, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Kaijun Niu
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Changes in Thyroid Hormone Levels Within the Normal and/or Subclinical Hyper- or Hypothyroid Range Do Not Affect Circulating Irisin Levels in Humans
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Case Report

A Case Report of Hajdu-Cheney Syndrome.: Eun Jin Han, Jun Il Mun, So Yeon An, Yun Jung Jung, Ok Hwa Kim, Yoon Sok Chung; Endocrinol Metab. 2010;25(2):152-156. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.152

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Abstract PDF

Hajdu-Cheney syndrome (HCS) is a rare skeletal dysplasia that is characterized by acroosteolysis of the distal phalanges, distinctive craniofacial and skull changes, dental abnormalities and generalized osteoporosis. The clinical and radiologic characteristics are variable and these characteristics progress with age. This syndrome shows autosomal dominant inheritance with sporadic cases. The genetic defects or molecular pathogenesis of HCS are still unknown. We experienced a case of Hajdu-Cheney syndrome in a 20-year-old man who had generalized osteoporosis with multiple non-traumatic spine compression fractures. He had acroosteolysis of the hands and feet, wormian bones in the skull, facial dysmorphism (mid-facial flattening, micrognathia and bushy eyebrows), a high arched palate, malocclusion and short dental alveolar processes. HCS was diagnosed based on the clinical and radiologic evidence. For the differential diagnosis, we excluded the other possible causes of the acroosteolysis and wormian bones, including hyperparathyroidism, osteogenesis imperfecta, hypophosphatemia and mandibuloacral dysplasia. The specific treatment of HCS is unknown, but case reports with bisphosphonate treatment have been reported.

Citations

Citations to this article as recorded by

Band acro-osteolysis in a Black woman: a case report and review of the literature
Jin-Myoung Dan, Cheungsoo Ha, Ho-Jae Lee
Archives of Hand and Microsurgery.2022; 27(1): 62. CrossRef
Clinical consequences in truncating mutations in exon 34 of NOTCH2: Report of six patients with Hajdu–Cheney syndrome and a patient with serpentine fibula polycystic kidney syndrome
Yoko Narumi, Byung‐Joo Min, Kenji Shimizu, Itsuro Kazukawa, Kiyoko Sameshima, Koichi Nakamura, Tomoki Kosho, Yumie Rhee, Yoon‐Sok Chung, Ok‐Hwa Kim, Yoshimitsu Fukushima, Woong‐Yang Park, Gen Nishimura
American Journal of Medical Genetics Part A.2013; 161(3): 518. CrossRef
An Unusual Presentation of Diabetic Ketoacidosis in Familial Hajdu-Cheney Syndrome: A Case Report
Gil-Ho Lee, So-Yeon An, Young Bae Sohn, Seon-Yong Jeong, Yoon-Sok Chung
Journal of Korean Medical Science.2013; 28(11): 1682. CrossRef
Effect of Zoledronic Acid on Acro-Osteolysis and Osteoporosis in a Patient with Hajdu-Cheney Syndrome
Sena Hwang, Dong Yoeb Shin, Seong Hwan Moon, Eun Jig Lee, Sung-Kil Lim, Ok Hwa Kim, Yumie Rhee
Yonsei Medical Journal.2011; 52(3): 543. CrossRef

Original Article

Impaired Metabolic Signal Transduction Networks in Isolated Skeletal Muscle in Korean type 2 Diabetic Patients.: Joon Hyuck Choi, Kwan Woo Lee, Hyo Jeong Kim, Dong Hun Lee, Jong Woo Lee, Jung Eun Kim, Hyun Chae Yim, Kyung Mi Kim, Sung Yi Choi, Yoon Sok Chung, Hyeon Man Kim; J Korean Endocr Soc. 2002;17(5):685-697. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-beta), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes (n=9) and control subjects (n=11). METHODS: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphorylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-beta), Akt and GSK-3. RESULT: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA1c in controls and diabetic patients were 98.+/-1.3 and 208.1+/-16.5 ng/dl, and 5.4+/-0.5 and 9.2+/-0.6%, and 1.4+/-0.2 in the control subjects, and 72.2+/-52.3% (p<0.01) and 10.2+/-6.3 (p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp tests were 8.2+/-0.6 mg/kg/min and 3.7+/-1.1 ng/kg/min in the control subjects and in the diabetic patients, respectively (p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively (p<0.05). CONCLUSION: In korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus

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