Gut microbiota reshaped by exercise improved glycolipid metabolism in obese mice via increasing the production of medium and long chain fatty acids: A multi-omics study.

Exercise is effective in combating obesity and regulating the composition of the gut microbiota. However, the molecular mechanism by which exercise alters gut microbiota and its metabolites to exert weight loss has not been fully elucidated. In this study, the effect and mechanism of gut microbiota and microbial metabolites reshaped by exercise on weight loss were investigated by macrogenomic sequencing, metabolomics analysis and fecal microbiota transplantation (FMT). The results showed that exercise significantly increased the abundance of beneficial bacteria such as Oscillibacter, Lachnoclostridium, and unclassified_f__Lachnospiraceae, and decreased the abundance of Lactobacillus and Desulfovibrio. Meanwhile, exercise significantly increased medium- and long-chain fatty acid (MCFA and LCFA) content and decreased d-fructose levels. These metabolites were associated with fatty acid degradation and unsaturated fatty acid synthesis pathways. In addition, FMT from exercised mice significantly reduced high-fat diet (HFD)-induced obesity and lipid accumulation, increased insulin sensitivity, and improved glucose homeostasis, with decreased the levels of serum lipids and lipopolysaccharide (LPS). FMT also attenuated hepatic and pancreatic dysfunction, as well as hepatic steatosis. Notably, FMT from exercised mice significantly increased the content of MCFAs and LCFAs in the intestines of HFD-treated mice and upregulated the expression of genes related to glycolipid metabolism and the secretion of glucagon-like peptide-1 (GLP-1). Finally, caprylic, lauric, cardamic and stearic acids can significantly increase GLP-1 levels in Caco-2 cells. Taken together, exercise could reshape the intestinal microbiota to promote the production of MCFAs and LCFAs, thereby upregulating GLP-1 secretion, and ultimately improving glycolipid metabolism and alleviating obesity.