| Background: The number of obese people is on the rise.It is estimated that by 2030,more than 1.2 billion people will be obese in the world.and the obesity population is getting younger and younger.Moreover,obesity and its complications have a serious impact on people’s physical and mental health,and a huge economic burden on families,societies and countries.And clinically used to treat weight loss drugs are mostly western medicine,and side effects are large.Chinese herbal medicine has attracted much attention due to its multi-target,multi-component,and few side effects.Oleanolic acid is a pentacyclic triterpenoid contained in many plants,with a wide range of pharmacological activity,with anti-inflammatory,hypoglycemic lipid,anti-atherosclerosis and anti-diabetes effect.However,at present,the specific mechanism of oleanolic acid for reducing lipid and weight loss is not very clear,and there are few studies on whether lipid-lowering and weight loss can be achieved by improving intestinal flora.Therefore,to enrich the research on lipid-lowering mechanism of oleanolic acid and its effect on intestinal flora,and provide theoretical research basis for the application of oleanolic acid lipid-lowering weight loss drugs or health care products.Objective: To investigate the effects of oleanolic acid on PPARγ and TGR5 in adipose tissue and intestinal microflora of obese mice from animal level,so as to inhibit fat synthesis and reduce inflammation to improve obesity.It is of great significance to explore the mechanism of oleanolic acid in treating obesity.Methods: Four-week-old C57BL/6 mice were randomly divided into control group and high-fat diet group,and the weight of the mice was weighed weekly.After 10 weeks,the serum levels of fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL-C)and high-density lipoprotein(HDL-C)were detected in the two groups of mice.Mice whose obesity model was successfully established were selected and divided into model group,positive drug orlistat group,and oleanolic acid low-dose,medium-dose and high-dose groups,and were given drug intragastric intervention for 4 weeks.the eyeballs were bled and the mice were sacrificed by decapitation.Blood glucose and lipid levels were detected in each group.HE staining was used to observe the morphological changes of liver and adipose tissue in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect tumor factor α(TNF-α),interleukin 6(IL-6),mononuclear chemotactic protein 1(MCP-1),and glucagon-like peptide 1(GLP-1).Western blot was used to detect the expression of TGR5,PPARγ,SREBP1 and UCP1 proteins in mouse adipose tissue.16 s sequencing was performed on the intestinal contents of mice to analyze the composition and abundance of intestinal flora.Results: Compared with the normal group,the body weight of the mice in the high-fat feeding group for 10 weeks continued to increase,and the levels of blood glucose and blood lipids increased.After 4 weeks of oral administration of oleanolic acid,compared with the model group,oleanolic acid could significantly reduce the body weight and serum TC,TG,LDL-C,and FBG content of obese mice,and increase HDL-C content.Oleanolic acid can also significantly reduce the levels of TNF-ɑ,IL-6 and MCP-1 in serum of obese mice,and increase serum GLP1 levels,and improve the morphology of liver and adipose tissue of obese mice.Oleanolic acid also significantly increased the expression of TGR5 and decreased the expression of PPARγ and SREBP-1 in adipose tissue of mice.16 S sequencing showed that oleanolic acid could improve the species composition and abundance of intestinal flora.Conclusion: Oleanolic acid may improve the glucose and lipid metabolism disorder in obese mice by down-regulating the expression of PPARγ and SREBP1,and up-regulating the expression of TGR5 to reduce the low-grade inflammation caused by obesity,and improve the species composition and abundance of intestinal flora. |
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