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Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk

文献类型：期刊论文

作者Song, Yeyu1,2; Liu, Yameng1; Jiang, Jie1; Zheng, Youjie3; Wang, Zixuan2; Xie, Cen1; Fan, Jian-Gao2,3
刊名JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
出版日期2026-01-07
页码16
关键词Sarcopenia Metabolic dysfunction-associated steatotic liver dis-ease Mendelian randomization Liver-muscle crosstalk C-C motif chemokine ligand 2 Adrenomedullin
ISSN号2225-0719
DOI10.14218/JCTH.2025.00538
英文摘要Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. This study aimed to investigate whether a bidirectional causal link exists between MA-SLD and sarcopenia and to identify the molecular mediators involved in liver-muscle crosstalk. Methods: We applied Mendelian randomization to test the causal effect of sarcopenia-related traits on MASLD risk. To capture distinct clinical features, we established complementary mouse models, including diet-induced and genetic (ob/ob) MASLD models, a stelic animal model, and a drug-induced muscle atrophy model. Multi-tissue transcriptomic profiling was performed on liver and muscle to uncover altered pathways. Results: Complementing prior genetic evidence establishing MASLD as a causal factor for sarcopenia, our Mendelian randomization analysis revealed that diminished muscle mass and muscle function contribute to an elevated risk of MASLD. In mice with MASLD, we observed loss of muscle mass, reduced strength, and ectopic lipid deposition in skeletal muscle. Conversely, muscle atrophy exacerbated hepatic steatosis, inflammation, and fibrosis in MASLD mice. Transcriptional profiling revealed that sarcopenia impairs hepatic metabolic homeostasis by enhancing fatty acid uptake and impairing oxidative phosphorylation, while MASLD, in turn, promotes muscle dysfunction by exacerbating inflammatory responses and metabolic dysfunction. We further identified C-C motif chemokine ligand 2 as a key myokine that drives MASLD, and adrenomedullin as a key hepatokine that triggers sarcopenia. Conclusions: Our findings suggest a potential bidirectional causal relationship between MASLD and sarcopenia, which may be partially mediated by C-C motif chemokine ligand 2 and adrenomedullin.
WOS关键词NONALCOHOLIC STEATOHEPATITIS ; ADRENOMEDULLIN ; OBESITY ; EXPRESSION ; NAFLD ; NASH
资助项目Noncommunicable Chronic Diseases-National Science and Technology Major Project[2023ZD0508700] ; National Key Research and Development Program of China[2021YFA1301200] ; National Natural Science Foundation of China[82222071] ; National Natural Science Foundation of China[82170593] ; National Natural Science Foundation of China[82470600] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830402]
WOS研究方向Gastroenterology & Hepatology
语种英语
WOS记录号WOS:001658985100001
出版者XIA & HE PUBLISHING INC
源URL[http://119.78.100.183/handle/2S10ELR8/322593]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Xie, Cen; Fan, Jian-Gao
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Gastroenterol, Sch Med,Ctr Fatty Liver, Shanghai, Peoples R China
3.Shanghai Key Lab Pediat Gastroenterol & Nutr, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Song, Yeyu,Liu, Yameng,Jiang, Jie,et al. Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk[J]. JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY,2026:16.
APA Song, Yeyu.,Liu, Yameng.,Jiang, Jie.,Zheng, Youjie.,Wang, Zixuan.,...&Fan, Jian-Gao.(2026).Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk.JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY,16.
MLA Song, Yeyu,et al."Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk".JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY (2026):16.

入库方式： OAI收割

来源：上海药物研究所

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