Betulinic acid alleviates body fat accumulation and dyslipidemia by inhibiting de novo lipogenesis and stimulating lipolysis in vivo

Abstract

Betulinic acid (BA), derived from natural substances especially birch wood bark, is a pentacyclic triterpenic acid. BA has beneficial bioactive effects as an antagonist for tumors, HIV and oxidants. Studies on BA effects against obesity and dyslipidemia have not clearly clarified the lipogenic pathway. This research hypothesized that betulinic acid would improve body fat and dyslipidemia in vivo. Male C57BL/6 mice were randomly assigned to five groups as follows: 1) high cholesterol diet (HCLD, 45% kcal from fat, 1.25% cholesterol) as control, 2) fenofibrate (150 mg/kg b.w + HCLD) as positive control 3) BA5 (BA 5 mg/kg b.w + HCLD), 4) BA15 (BA 15 mg/kg b.w + HCLD) and 5) BA25 (BA 25 mg/kg b.w + HCLD). BA was orally administered for 12 weeks. Body weight of BA25 was decreased compared to the control from 2 weeks to 12 weeks (p < 0.05 and p < 0.01). Fat mass was reduced by approximately 32% in all BA treatment groups (p < 0.05 and p < 0.001). Serum triglyceride was improved by all BA treatments (p < 0.001). Free fatty acid was reduced by all BA treatment groups (p < 0.01 for BA 25). Total cholesterol was diminished by all BA treatments (p < 0.001). LDL‐cholesterol was reduced by BA5 and BA15 (p < 0.05, p < 0.01 respectively). Acetyl‐CoA carboxylase1, a lipogenic enzyme in the liver, was inactivated by BA treatments (p < 0.001 for BA25). Stearoyl CoA desaturase was decreased by BA15 and BA25 (p < 0.01 and p < 0.05 respectively). Fatty acid synthase and sterol regulatory element‐binding protein 1 were reduced by BA although not significantly. Lipase, an enzyme related to lipolysis in white adipose tissue, was increased by BA15 and BA25 (p < 0.01 and p < 0.05 respectively). Phosphorylation hormone sensitive lipase was increased by BA5 (p < 0.01). Inactivating low‐density lipoprotein receptor‐related protein 6 in liver, which plays a major role in lipid homeostasis, was increased by BA25 (p < 0.001). Major factors of dyslipidemia in serum were alleviated by inhibiting lipogenesis in liver and increasing lipolysis in white adipose tissue. It was confirmed that BA is a potential compound for prevention and treatment of metabolic diseases caused by obesity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.