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

Abstract

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 β-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.

Oat avenanthramide B alleviates high-fat diet-induced obesity via regulating fatty acid metabolism involved in gut bacteria and fungi remodeling

“…FATP4 is also believed to play a role in FA uptake, as the knockdown of FATP4 in primary mice's small intestinal epithelial cells resulted in reduced FA uptake [28] . Following absorption by intestinal cells, FAs are transported to the endoplasmic reticulum via microsomal triglyceride transfer protein (MTTP) and then packaged with apolipoproteins (such as ApoB, ApoA-I, and ApoA-IV) to form CM [28,29] . This study found that AVN B can inhibit the expression of CD36, FATP4, and ApoA-IV.…”

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

“…In mice, dietary fiber with insulin altered the composition of the microbiota and the levels of microbiota-derived metabolites, notably bile acids, that triggered type 2 inflammation at barrier surfaces [10,26]. Some special diets, such as methionine-restricted diets (MRDs) and l-Glutamine, enhanced the intestinal barrier integrity by regulating the intestinal microbiota and bile acids profiles [27,28]. And a BAR signaling-independent, physicochemical mechanism for conjugated the BA-mediated protection of epithelial barrier function was described.…”

The essential role of glutamine metabolism in diabetic cardiomyopathy: A review

“…Furthermore, glutamine administration has been shown to suppress inflammation by inhibiting the activation of NLRP3 and modulating cell pyroptosis. [80,81] Zhang et al [82] demonstrated that inhibition of glutaminolysis can inhibit the activation of the NLRP3/caspase-1/IL-1β pathways. The activation of JNK is dependent on the phosphorylation of JNK, while treatment with Gln can decrease the phosphorylated JNK by attenuating inflammation.…”