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18 "Sarcopenia"
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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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AbstractAbstract PDFSupplementary MaterialPubReader   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.
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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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AbstractAbstract PDFSupplementary MaterialPubReader   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.
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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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AbstractAbstract PDFPubReader   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.
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Miscellaneous
Protective Effect of Delta-Like 1 Homolog Against Muscular Atrophy in a Mouse Model
Ji Young Lee, Minyoung Lee, Dong-Hee Lee, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Endocrinol Metab. 2022;37(4):684-697.   Published online August 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.1446
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy.
Methods
We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes.
Results
Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway.
Conclusion
DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.
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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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  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Mechanism and physical activities in bone-skeletal muscle crosstalk
    Zhonghan Zhao, Kai Yan, Qiao Guan, Qiang Guo, Can Zhao
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue
    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
  • Role of the Osteocyte in Musculoskeletal Disease
    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
    Biochemical Pharmacology.2023; 215: 115694.     CrossRef
  • Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk
    Liu Guo, Menchus Quan, Weijun Pang, Yulong Yin, Fengna Li
    Trends in Endocrinology & Metabolism.2023; 34(10): 666.     CrossRef
  • Sclerostin: clinical insights in muscle–bone crosstalk
    Antimo Moretti, Giovanni Iolascon
    Journal of International Medical Research.2023;[Epub]     CrossRef
  • Anti-sclerostin antibodies: a new frontier in fragility fractures treatment
    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
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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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  • 184 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • 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
  • 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.2023;[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
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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
  • 4,167 View
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  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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
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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
  • 3,595 View
  • 134 Download
  • 1 Web of Science
  • 2 Crossref
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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  • A review of radiological definitions of sarcopenia in cancer
    James W. Wang, Jiarong Chen, Alison H. McGregor, Matthew Williams
    JCSM Clinical Reports.2023; 8(2): 36.     CrossRef
  • Weight‐adjusted waist as an integrated index for fat, muscle and bone health in adults
    Kyoung Jin Kim, Serhim Son, Kyeong Jin Kim, Sin Gon Kim, Nam Hoon Kim
    Journal of Cachexia, Sarcopenia and Muscle.2023; 14(5): 2196.     CrossRef
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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
  • 4,080 View
  • 109 Download
  • 7 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

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  • Molecular mechanisms underlying sarcopenia in heart failure
    Cody A. Rutledge
    The Journal of Cardiovascular Aging.2024;[Epub]     CrossRef
  • Role of glucocorticoid and mineralocorticoid receptors in rainbow trout (Oncorhynchus mykiss) skeletal muscle: A transcriptomic perspective of cortisol action
    Jorge E. Aedo, Rodrigo Zuloaga, Daniela Aravena-Canales, Alfredo Molina, Juan Antonio Valdés
    Frontiers in Physiology.2023;[Epub]     CrossRef
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    Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina, Juan Antonio Valdés
    Genes.2023; 14(2): 512.     CrossRef
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    Yasuhiro Izumiya
    Circulation Journal.2023; 88(1): 20.     CrossRef
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    Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
    Endocrinology and Metabolism.2023; 38(6): 597.     CrossRef
  • 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
    Endocrinology and Metabolism.2023; 38(6): 701.     CrossRef
  • The Role of Aldosterone in OSA and OSA-Related Hypertension
    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
  • Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease
    Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
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
  • 8,599 View
  • 328 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.

Citations

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  • The Current Landscape of Pharmacotherapies for Sarcopenia
    Gulistan Bahat, Serdar Ozkok
    Drugs & Aging.2024; 41(2): 83.     CrossRef
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    Yining Liu, Xiangliang Liu, Linnan Duan, Yixin Zhao, Yuwei He, Wei Li, Jiuwei Cui
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    Saniya Khan, Sunil Kumar, Sourya Acharya, Anil Wanjari
    Journal of Health and Allied Sciences NU.2023; 13(04): 453.     CrossRef
  • Novel Potential Targets for Function-Promoting Therapies: Orphan Nuclear Receptors, Anti-inflammatory Drugs, Troponin Activators, Mas Receptor Agonists, and Urolithin A
    Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob van Maanen, Roger A Fielding, Lewis A Lipsitz
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    Jong Hyeon Yoon, Seung-Min Lee, Younglang Lee, Min Ju Kim, Jae Won Yang, Jeong Yi Choi, Ju Yeon Kwak, Kwang-Pyo Lee, Yong Ryoul Yang, Ki-Sun Kwon
    Biochemical and Biophysical Research Communications.2022; 586: 157.     CrossRef
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    Takahiro Eguchi, Yuji Yamanashi
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    Hsien-Hao Huang, Tse-Yao Wang, Shan-Fan Yao, Pei-Ying Lin, Julia Chia-Yu Chang, Li-Ning Peng, Liang-Kung Chen, David Hung-Tsang Yen
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Close layer
Original Articles
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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  • 155 Download
  • 12 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

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Close layer
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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  • 3 Web of Science
  • 4 Crossref
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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    Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li
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    Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li
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    Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim
    Endocrinology and Metabolism.2021; 36(4): 865.     CrossRef
Close layer
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
  • 21,864 View
  • 1,238 Download
  • 72 Web of Science
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AbstractAbstract PDFPubReader   ePub   
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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Close layer
Original Article
Clinical Study
Relationship of Sarcopenia with Microcirculation Measured by Skin Perfusion Pressure in Patients with Type 2 Diabetes
Chan-Hee Jung, Yoon Young Cho, Dughyun Choi, Bo-Yeon Kim, Chul-Hee Kim, Ji-Oh Mok
Endocrinol Metab. 2020;35(3):578-586.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.679
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients.
Methods
In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, <7 kg/m2; women, <5.7 kg/m2) using BIA. We divided the participants into two groups based on SPP (≤50 and >50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation.
Results
Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP >50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors.
Conclusion
These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

Citations

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Close layer
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
  • 10,347 View
  • 285 Download
  • 63 Web of Science
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AbstractAbstract PDFPubReader   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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