Sennoside A Improves Mitochondrial Function of Large Intestine in Diet-Induced Obese Mice to Preserve GLP-1 Expression through Induction of Short-Chain Fatty Acids

Abstract

Objective: Sennoside A (SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative. However, its activity remains unknown in the regulation of GLP-1 expression. Here, we investigated the possibility in high-fat-diet (HFD) induce obesity (DIO) mice. Methods: SA was administrated in DIO mice through dietary supplementation for 8 weeks. In the study, energy balance and insulin sensitivity were monitored. GLP-1 was determined in plasma and colon tissue. Mitochondria were examined in structure by transmission electron microscopy and in function with Seahorse XF24 in the colon tissue. Gut microflora was examined using fecal DNA and the diversity of gut microbiota was analyzed by Miseq sequencing. The fecal short chain fatty acids (SCFAs) were examined by GC (gas chromatograph). Results: There was an increase in cell necrosis in the epithelial layer of mucosa of DIO mice, which was observed with reduction of plasma GLP-1 and mRNA expression in the colon tissue. Mitochondria exhibited an increase in size and membrane rupture in the epithelial cells. An elevation in the complex I activity, and a fall in the complex II activity were observed in the mitochondria, suggesting an imbalance of the complex I/II in the cells. The short chain fatty acids were decreased in abundance along with the dysbiosis in the colon of DIO mice. All of those alterations were corrected by SA in DIO mice along with control of obesity and insulin resistance. Conclusion: The data suggested that SA may improve GLP-1 expression in colon through restoration of mitochondrial function and structure in the epithelia cells of mucosal. The effect may be related to restoration of gut microflora/SCFAs axis. Disclosure J. Le: None. J. Ye: None. Y. Sun: None.