| Background: Obesity is a chronic metabolic disease,Obesity can increase the incidence of hypertension,diabetes,coronary heart disease,tumor and other diseases,which seriously threatens people’s quality of life and causes a huge burden on medical treatment and social economy.Alisma has a good therapeutic effect on obesity,hyperlipidemia and fatty liver disease,and its extract can regulate lipid metabolism by changing the abundance,diversity and functional group of intestinal flora.alisol B23-acetate has a variety of effects such as lowering blood glucose and lipid,protecting liver,anti-bacterial and anti-cancer,etc.It has been used in the treatment of inflammation and metabolic diseases,but there are few studies on its effect on glucose and lipid metabolism disorders caused by obesity.Therefore,it is of great significance to explore the effect and mechanism of alisol B 23-acetate on obesity-induced glucose and lipid metabolism disorders,and to provide experimental basis for the development of Chinese medicine alismatol monomer for the prevention and treatment of obesity.Objective: To observe the effect of alisol B 23-acetate on high fat diet-induced obesity mice,and explore the mechanism of alisol B23-acetate regulates glycolipid metabolism disorder.Method: Sixty male C57BL/6J mice were randomly divided into normal group and model group,ten mice in the normal group were fed with normal diet,and fifty mice in the model group were fed with high-fat diet.Both groups were normal drinking water,and the obese mouse model was successfully copied after 10 weeks.The obese mice were divided into five groups according to body weight: model group,orlistat group,and alisol B 23-acetate low-dose,medium-dose and high-dose groups with ten mice in each group.The mice were given continuous administration for 4 weeks.Body weight and waist circumference were measured weekly,after the last administration,the body fat content of mice was analyzed by small animal MRI systemic composition analyzer;The blood glucose and blood lipids in the serum of mice were measured with a kit and an automatic analyzer;The pathomorphological changes of visceral fat and liver tissue in mice were observed by hematoxylin-eosin staining(HE staining);Observing the activity of peroxidase proliferator-activated receptor-γ(PPAR-γ),nuclear factor kappa-B(NF-κB)and mouse interleukin-6(IL-6)in liver tissues,and the TNF-α in the serumby enzyme-linked immunosorbent assay(ELISA).The protein expression levels of PPAR-γ in liver tissues were detected by Western blot.Finally,fecal samples of mice in each group were collected,and 16 S r RNA(V3+ V4)variable region of intestinal flora was sequenced by high-throughput sequencing.Changes in gut microbiota diversity of each group were analyzed,and differences in bacterial genera were identified by comparison between groups.Result: Compared with normal group,the body weight,waist circumference and the body fat content of the model group were significantly increased(P<0.01),Serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein-cholesterol(HDL-C),fasting blood glucose(GLU)levels were significantly increased(P<0.01),there was no significant difference in low density lipoprotein-cholesterol(LDL-C);The liver tissues and visceral adipose cells were significantly enlarged,the inflammatory cells were observed as focal infiltration and among them,hepatocytes are associated with steatosis by HE staining;while the NF-κB and IL-6activities in liver were significantly increased(P<0.01,P<0.05),and the PPAR-γ was significantly decreased in model group(P<0.05);Protein expression of PPAR-γ in liver were significantly increased in the model group(P<0.05).Compared with model group,different doses of alisol B 23-acetate can reduce the body weight,waist circumference and the body fat content of mice to varying degrees.Meanwhile alisol B 23-acetate can decrease the serum levels of TC,TG,and GLU,reduce liver and fat cell size and surface inflammation;and the PPAR-γ activity and protein expression levels in liver tissues were also increased,while NF-Κb,IL-6 in liver tissue and TNF-α in the serum activity were decreased(P<0.05,P<0.01).By Western blot,we also found that alisol B 23-acetate activated PPARγ.High-throughput sequencing of gut microbiota showed that alisol B 23-acetate could altere the composition of intestinal metabolites in obese mice,which was significantly different from that in the obesity model group,and played a certain role in regulating the composition of gut microbiota.Conclusion: Alisol B 23-acetate can significantly ameliorate the glycolipid metabolism disorder on high fat diet-induced obesity mice.Its mechanism to ameliorate glycolipid metabolism disorder is related to the regulation of PPAR-γ activity in liver tissues and to restrain the NF-κB,down-regulating the expression of downstream transcription factors to improve obesity.In addition,Alisol B 23-acetatecan improve the intestinal beneficial bactria and regulate the flora structure. |
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