Endocrinology and Metabolism

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

Citations to this article as recorded by

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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146 Download
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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.

Citations

Citations to this article as recorded by

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization
Mingchong Liu, Xiao Fu, Daqian Yu, Meng Li, Yutao Pan, Chensong Yang, Guixin Sun
Journal of Cachexia, Sarcopenia and Muscle.2024;[Epub] 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; : 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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