Diabetes, Metabolic Syndrome and Obesity (Aug 2022)
Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats
Abstract
Ying Ning,* Yanju Gong,* Tianyan Zheng, Ya Xie, Shiqing Yuan, Weijun Ding School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijun Ding; Shiqing Yuan, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Chengdu, 611137, People’s Republic of China, Tel + 86-28-61800219, Fax + 86-28-61800225, Email [email protected]; [email protected]: The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR.Methods: In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform.Results: Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats.Conclusion: We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.Keywords: insulin resistance, IR, lingguizhugan decoction, LGZGD, intestinal microbiota, nontargeted metabolomics, high-fat diet, HFD
