Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication.

Autor: Wang H; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Guo S; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Gao H; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Ding J; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Li H; Department of Sports Medicine and Arthroscopy Surgery, Huashan Hospital, Fudan University, Shanghai, China., Kong X; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Zhang S; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., He M; Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.; Shanghai Medical College, Fudan University, Shanghai, China., Feng Y; Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai, China., Wu W; Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China., Xu K; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Chen Y; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China., Zhang H; Shanghai Medical College, Fudan University, Shanghai, China., Liu T; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China.; Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.; School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China.., Kong X; State Key Laboratory of Genetic Engineering and School of Life Sciences, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai, China.; Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2024 Jun 18; Vol. 134 (16). Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1172/JCI178303
Abstrakt: Myostatin (MSTN) has long been recognized as a critical regulator of muscle mass. Recently, there has been increasing interest in its role in metabolism. In our study, we specifically knocked out MSTN in brown adipose tissue (BAT) from mice (MSTNΔUCP1) and found that the mice gained more weight than did controls when fed a high-fat diet, with progressive hepatosteatosis and impaired skeletal muscle activity. RNA-Seq analysis indicated signatures of mitochondrial dysfunction and inflammation in the MSTN-ablated BAT. Further studies demonstrated that Kruppel-like factor 4 (KLF4) was responsible for the metabolic phenotypes observed, whereas fibroblast growth factor 21 (FGF21) contributed to the microenvironment communication between adipocytes and macrophages induced by the loss of MSTN. Moreover, the MSTN/SMAD2/3-p38 signaling pathway mediated the expression of KLF4 and FGF21 in adipocytes. In summary, our findings suggest that brown adipocyte-derived MSTN regulated BAT thermogenesis via autocrine and paracrine effects on adipocytes or macrophages, ultimately regulating systemic energy homeostasis.
Databáze: MEDLINE