The Effect And Mechanism Of Betulinic Acid On Obesity

Objectives: Betulinic Acid has the known inhibitory pharmacological effects on tumor,virus and inflammatory,but the relationship between Betulinic Acid and metabolic diseases has rarely been reported.In this study,we will use animal models and cell models to demonstrate that the Betulinic Acid can treat obesity and improve lipid deposition in the liver.In addition,we will take the studies to explore the possible mechanism of Betulinic Acid.Methods: We conducted experiments both in vivo and in vitro.In vivo experiments,we performed the same operation in three different obese animal models,with or without feeding the standard chow diet containing Betulinic Acid for 2 months.During this period,we regularly monitor body weight,food intake and temperature.Metabolism cage was used to monitor the activity and energy metabolism of the animals.Micro PET-CT was used to assess the metabolic level of tissues.The glucose tolerance and insulin sensitivity of mice were monitored as well.After killing the mice,molecular biological analysis was performed on serum and tissue related to liver and adipose.In vitro experiments,we used Hep G2 cells and C3H10T1/2 cells to observe the effect of Betulinic Acid on them by using oil red O staining and monitoring the content of triglyceride in cells.Results: In diet induced obese mice animal experiments,Betulinic Acid could significantly reduce body weight and improve fatty liver.The various indexs of serum and liver tissue have also been significantly improved.Furthermore,the metabolic rate and the activity of brown adipose tissue(BAT)increased significantly.The results by electron microscope showed that mitochondrial number was significantly increased in various tissues in Betulinic Acid treated mice compared with the control and the mitochondrial DNA copy number(mt DNA)was increased evidently.In addition,the glucose tolerance and insulin resistance were improved evidently by Betulinic Acid treatment.But these positive effects were completely absent in db/db mice and ob/ob mice.In the cell experiment,the lipid accumulation was dose-dependent improved in both hepatocytes and adipocytes treated with Betulinic Acid.Conclusion: Combined with the results of vivo and in vitro experiments,the study could justify that Betulinic Acid promotes BAT function and drives the acquisition of functional brown-like adipocytes in the WAT,leading to increased energy expenditure,which can be used to treat obesity.Our findings will provide more data support and solutions for the rational use of Betulinic Acid in the treatment of obesity or as a precursor drug.