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

J Pharmacol Sci

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Published: December 2021

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 (Sirt1) mice, including WT-BDL, WT-sham, Sirt1-BDL and Sirt1-sham mice. Compared with WT-BDL mice, Sirt1-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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jphs.2021.09.003DOI Listing

Publication Analysis

Top Keywords

muscle wasting
20
cirrhotic mice
12
intestinal sirt1
8
sirt1 exacerbated
8
exacerbated muscle
8
short-chain fatty
8
increased intestinal
8
decrease abundance
8
scfa-producing bacteria
8
mice
7

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!