Endocrinology and Metabolism

Original Article

Mineral, bone & muscle
Muscle Loss Driven by Extracellular Signal-Regulated Kinase Suppression via β-Adrenergic Activation in High-Normal Catecholamine Status: Jieun Lee, Ju Yeon Kwak, Ho Yeop Lee, Ji Sun Moon, Hyo Ju Jang, Ha Thi Nga, Thi Linh Nguyen, Alfin Mohammad Abdillah, Junglyun Kim, Sihwan Kim, Yong Ryoul Yang, Jeong Eun Lee, Hyon-Seung Yi; Endocrinol Metab. 2026;41(2):319-332. Published online April 6, 2026; DOI: https://doi.org/10.3803/EnM.2025.2527

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Abstract PDF Supplementary Material PubReader ePub: Background
Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss.
Methods
This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis.
Results
Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation.
Conclusion
Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.

Brief Report

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

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Abstract PDF Supplementary Material PubReader ePub

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

Citations

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The role of sestrin2 in skeletal muscle regeneration after injury
Chae Young Hwang, Sang-Min Park, Hoyeon Lee, Seung-Min Lee, Jeong Yi Choi, Su-Jin Baek, Taeyoung Kim, Yong Ryoul Yang, Ki-Sun Kwon
The Korean Journal of Physiology & Pharmacology.2026; 30(1): 19. CrossRef
Sesn2 is Associated with Attenuated Muscle Atrophy and Altered Expression of Key Myogenic and Autophagy Markers in Mdx Mice
Zubiao Song, Qing Lin, Jiahui Liang, Juanjuan He, Weixi Zhang
Journal of Molecular Neuroscience.2026;[Epub] CrossRef
Age-related changes in adrenergic regulation of contractility and redox status of glycolytic and oxidative skeletal muscles
Julia G. Odnoshivkina, Guzel V. Sibgatullina, Svetlana A. Dmitrieva, Anastasia A. Ponomareva, Venera F. Khuzakhmetova, Ellya A. Bukharaeva, Alexey M. Petrov
GeroScience.2025;[Epub] CrossRef
Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation
Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye
Clinical and Experimental Hypertension.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
Frontiers in Endocrinology.2023;[Epub] CrossRef

Original Articles

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

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

Citations

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Biphasic regulation of myogenesis by ALDH2, aldosterone, and oxidative stress
José Emmanuel Martínez-Cortés, Maikel Valle-Clara, Damaso Fernández-Hernández, Guillermo Ávila
Pflügers Archiv - European Journal of Physiology.2026;[Epub] CrossRef
Therapeutic Potential of Mineralocorticoid Receptors in Skeletal Muscle Aging
Ricardo Aparecido Baptista Nucci, Otávio de Toledo Nóbrega, Wilson Jacob-Filho
Receptors.2025; 4(3): 13. CrossRef
A Narrative Review on Nitrate-Rich Diets as Adjuncts to Antihypertensive Therapy: Enhancing Treatment Efficacy via Oxidative Stress Modulation
Mila Silva-Cunha, Carla Speroni Ceron, Heitor Moreno, José Eduardo Tanus-Santos
Biomedicines.2025; 14(1): 39. CrossRef
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
Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle
Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina, Juan Antonio Valdés
Genes.2023; 14(2): 512. CrossRef
Heart Failure Medication and Muscle Wasting
Yasuhiro Izumiya
Circulation Journal.2023; 88(1): 20. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
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

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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Abstract PDF Supplementary Material PubReader 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.

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Mingchong Liu, Xiao Fu, Daqian Yu, Meng Li, Yutao Pan, Chensong Yang, Guixin Sun
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JHEP Reports.2023; : 100754. CrossRef
C–C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease
Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li
JHEP Reports.2023; 5(9): 100805. CrossRef
Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity
Jin-Young Lee, Da-Ae Kim, Eun-Young Kim, Eun-Ju Chang, So-Jeong Park, Beom-Jun Kim
International Journal of Molecular Sciences.2021; 22(9): 4717. CrossRef
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
Endocrinology and Metabolism.2021; 36(4): 865. CrossRef

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