Integrated omics analysis unraveled the microbiome-mediated effects of Yijin-Tang on hepatosteatosis and insulin resistance in obese mouse.

BACKGROUND: Gut microbiota play important roles in insulin homeostasis and the pathogenesis of non-alcoholic fatty liver diseases (NAFLD). Yijin-Tang (YJT), a traditional Korean and Chinese medicine, is used in the treatment of gastrointestinal diseases and obesity-related disorders such as insulin resistance (IR) and NAFLD. PURPOSE: Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile. METHODS: C57BL/6J mice were fed a normal chow diet (NC) or high-fat/high-cholesterol (HFHC) diet with or without YJT treatment. Hepatic lipid profiles were analyzed using liquid chromatography/mass spectrometry, and the composition of gut microbiota was investigated using 16S rRNA sequencing. Then, hepatic lipid profiles, gut microbiome, and inflammatory marker data were integrated using multivariate analysis and bioinformatics tools. RESULTS: YJT improved NAFLD, and 39 hepatic lipid metabolites were altered by YJT in a dose-dependent manner. YJT also altered the gut microbiome composition in HFHC-fed mice. In particular, Faecalibaculum rodentium and Bacteroides acidifaciens were altered by YJT in a dose-dependent manner. Also, we found significant correlation among hepatic phosphatidylglycerol metabolites, F. rodentium, and γδ-T cells. Moreover, interleukin (IL)-17, which is secreted by the γδ-T cell when it recognizes lipid antigens, were elevated in HFHC mice and decreased by YJT treatment. In addition, YJT increased the relative abundance of B. acidifaciens in NC or HFHC-fed mice, which is a gut microbiota that mediates anti-obesity and anti-diabetic effects by modulating the gut environment. We also confirmed that YJT ameliorated the gut tight junctions and increased short chain fatty acid (SCFA) levels in the intestine, which resulted in improved IR. CONCLUSION: These data demonstrated that gut microbiome and hepatic lipid profiles are regulated by YJT, which improved the IR and NAFLD in mice with diet-induced obesity.

Effect of Er Chen Tang on CYP2E1 and Mitochondrial Energy Metabolism in Nonalcoholic Fatty Liver Disease / 中国药师

Objective:To observe the effect of Er Chen Tang on CYP2E1 and mitochondrial energy metabolism in nonalcoholic fat-ty liver disease ( NAFLD) to explore the role of Pinellinae Rhizoma Praeparata ( PRP) and Citri reticulatae pericarpium ( CRP) in the treatment of nonalcoholic fatty liver disease. Methods:Er ChenTang and the prescription without PRP or CRP was respectively given the animal models by gastric gavage. The serum levels of ALT, AST, triglyceride, cholesterol, SOD and MDA in hepatic tissue, and the contents of liver tissue CYP2E1 and ATP were detected in the mice. Results:The CYP2E1 levels in NAFLD mice increased signif-icantly with abnormal mitochondrial energy metabolism. Compared with those in the model group, the levels of ALT, AST, triglyceride and cholesterol were significantly reduced by Er Chen Tang, meanwhile, the content of CYP2E1 was reduced and also restored liver en-ergy metabolism. The treatment effect significantly decreased when the lack of PRP or CRP, and the ability of restoring liver mitochon-drial energy metabolism of Er Chen Tang decreased significantly when the lack of PRP (P<0. 05). After the removal of CRP, the in-hibition ability of Er Chen Tang to CYP2E1 levels significantly decreased (P<0. 05). Conclusion:Er Chen Tang can effectively im-prove nonalcoholic fatty liver diseases, and effectively reduce the content of CYP2E1 in liver tissue of mice and restore the mitochondri-al energy metabolism.