Preventive Effects of L-Glutamine on High-Fat Diet-Induced Metabolic Disorders Linking with Regulation of Intestinal Barrier Integrity, Hepatic Lipid Metabolism, and Gut Microbiota in Rats

The present study was conducted to investigate the effects of L-glutamine (Gln) on a high-fat diet (HFD)-induced lipid metabolic abnormality and explore its possible mechanisms. The results demonstrated that Gln administration reduced body weight, improved serum lipids, and decreased glucose tolerance in HFD-fed rats. Meanwhile, Gln administration alleviated liver injury, reduced the hepatic inflammatory response by inhibiting NLRP3 inflammasome activation, and decreased hepatic lipid accumulation by promoting VLDL secretion and fatty acid beta-oxidation, as well as reduced bile acid synthesis by activating hepatic and ileal FXR in HFD-fed rats. Moreover, Gln administration restored HFD-induced intestinal barrier dysfunction, promoted intestinal fat absorption, suppressed intestinal inflammation, and also reshaped the gut microbiota composition in HFD-fed rats by downregulating the abundance of potential pathogens Escherichia-Shigella and upregulating the abundance of beneficial bacteria such as Akkermansia. To conclude, the present results showed that Gln may be a potential option for preventing HFD-induced metabolic disorders via the gut-liver axis.