Regulation of microbiota–GLP1 axis by sennoside A in diet-induced obese mice

In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota–GLP1 axis to improve glucose metabolism in the obese mice.Graphical abstractSennoside A (SA) activity was found in the improvement of insulin sensitivity in diet-induced obesity mice through restoration of blood level of glucagon-like peptide 1. SA induced Glp1 gene expression in L-cells of the colon tissue, which was associated with improvement of dysbiosis, short chain fatty acid abundance and mitochondrial function of L-cells.
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research