Suppression of Hepatic Lipogenesis and Enhancement of β-oxidation in Skeletal Muscle by Betulinic Acid Lead to the Reduction of Body Adiposity and Dyslipidemia in Mice (P21-043-19). (13th June 2019)

• Record Type: Journal Article
• Authors: Kim, Hyun Kyung; Go, Gwang-woong
• Is Part Of: Current developments in nutrition. Volume 3(2019)Supplement 1
• Publication Date: 2019-06-13
• Subjects: Nutrition -- Periodicals; Nutritional Physiological Phenomena; Nutrition; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 612.3
• DOI: 10.1093/cdn/nzz041.P21-043-19
• Languages: English
• ISSNs: 2475-2991

Abstract

Abstract: Objectives: Betulinic acid (BA) exists as a lipophilic conformation in nature, rich in fruits and vegetables, especially the bark of birch wood. Beneficial effects of BA on cancer, oxidative stress, and inflammation were previously reported. Studies of BA for anti-obesity and dyslipidemia have been recently emerged, however the outcomes are still not conclusive. We tested if BA improves obesity and/or dyslipidemia by incorporated mechanism of liver and skeletal muscle in vivo . Methods: Five-week-old male C57BL/6 mice were fed Western type diet (45% kcal from fat with 1.25% cholesterol) ad libitum for 12 weeks. Mice were allocated into five groups: (−) control, BA 5 mg/kg, BA 15 mg/kg, BA 25 mg/kg, and fenofibrate as a (+) control. BA was orally administered every day. For proved phenotype alteration, we analyzed mRNA and protein expressions linked to lipogenesis and β-oxidation. Results: Growth performance including final body weight, weight gain, and feed intake were not altered by BA. Body fat mass was decreased by all BA treated groups ( P < 0.01) without changes of lean mass. Energy expenditure contributed by β-oxidation was increased by BA 25 ( P < 0.001). Serum lipid profiles including triglyceride, free fatty acid, total cholesterol, and LDL cholesterol were significantly improved by all BA treated groups ( P < 0.001). Lipid accumulation in the liver was reduced by BA 15 and 25 (all P < 0.001). The mRNA expressions of Acc1and Scd1were dose-dependently suppressed by betulinic acid in liver ( P < 0.05). SREBP1 was diminished by BA treated groups (all P < 0.05). FAS showed reduced tendency by BA ( P = 0.06). In protein levels, ACC1 and SCD1 were inhibited by BA treated groups ( P < 0.001 and P < 0.05). FAS and SREBP1 tended to be reduced by BA ( P = 0.40 and P = 0.70). LPL and CPT1, β-oxidation markers in skeletal muscle, were activated by BA 25 ( P < 0.001 and P < 0.01). The activation of CPT1 was influenced by stimulating of AMPK-pT172 and ACC1-pS79 (all P < 0.05). Taken together, BA inhibitedde novolipogenesis in the liver and upregulated key proteins related to β-oxidation in skeletal muscle, contributing to the prevention of obesity and dyslipidemia. Conclusions: We suggest that BA is a potent nutraceutical for prevention and treatment of chronic metabolic diseases including obesity and dyslipidemia. Funding Sources: National Research Foundation of Korea.