Deletion of intestinal SIRT1 exacerbated muscle wasting in cirrhotic mice by decreasing the intestinal concentration of short-chain fatty acids and inflammation

Chien Fu Hsu, Chia Chang Huang, Tze Tze Liu, Ueng Cheng Yang, Chih Wei Liu, Shiang Fen Huang, Ying Ying Yang*, Yi Hsiang Huang, Ming Chih Hou, Han Chieh Lin

*此作品的通信作者

研究成果: Article同行評審

摘要

Systemic sirtuin 1 (SIRT1) activation alleviates muscle wasting and improves muscle function by downregulation of myotropic and proteolytic markers. In this study, we evaluated the effects of the intestinal Sirt1 deletion on the dysregulated gutmuscle axis in cirrhotic mice. Cirrhosis-related muscle wasting was induced by common bile duct ligated (BDL) in either wild-type (WT) or intestine-specific Sirt1-deleted (Sirt1IEC-KO) mice, including WT-BDL, WT-sham, Sirt1IEC-KO-BDL and Sirt1IEC-KO-sham mice. Compared with WT-BDL mice, Sirt1IEC-KO-BDL mice showed worsened low lean mass, exacerbated muscle wasting, increased expression of myotropic markers, increased muscular protein degradation, and decreased expression of myogenic markers through aggravation of intestinal inflammation (as evidenced by increased fecal calprotectin/lipocalin-2 levels, increased intestinal macrophage infiltration, and increased intestinal TNFα/IL-6 levels), decrease in abundance of short-chain fatty acid (SCFA)-producing bacteria, decrease in levels of intestinal SCFAs (with anti-inflammatory effects), and downregulation of SCFA receptor GPR43. In biliary cirrhotic mice, a decrease in the abundance of SCFA-producing bacteria and an increase in the levels of intestinal/muscular inflammatory markers are involved in the pathogenesis of dysregulated gut-muscle axis-related muscle wasting, and intestinal deletion of Sirt1 exacerbated these changes.

原文English
頁(從 - 到)376-385
頁數10
期刊Journal of Pharmacological Sciences
147
發行號4
DOIs
出版狀態Published - 12月 2021

指紋

深入研究「Deletion of intestinal SIRT1 exacerbated muscle wasting in cirrhotic mice by decreasing the intestinal concentration of short-chain fatty acids and inflammation」主題。共同形成了獨特的指紋。

引用此