K-D Kim1, H-Y Jung2, H G Ryu3, B Kim4, J Jeon2, H Y Yoo5, C H Park6, B-H Choi7, C-K Hyun1, K-T Kim8, S Fang9, S H Yang10, J-B Kim11. 1. School of Life Science, Handong Global University, Pohang, Gyungbuk, South Korea. 2. Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang, Gyungbuk, South Korea; R&D Center, NovMetaPharma Co., Ltd., Pohang, Gyungbuk, South Korea. 3. Department of Life Sciences, POSTECH, Pohang, Gyungbuk, South Korea. 4. School of Life Science, Handong Global University, Pohang, Gyungbuk, South Korea; R&D Center, NovMetaPharma Co., Ltd., Pohang, Gyungbuk, South Korea. 5. Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang, Gyungbuk, South Korea. 6. Mistle Biotech Co., Ltd., Pohang, Gyungbuk, South Korea. 7. Advanced Bio Convergence Center, Pohang Technopark, Pohang, Gyungbuk, South Korea. 8. Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang, Gyungbuk, South Korea; Department of Life Sciences, POSTECH, Pohang, Gyungbuk, South Korea. 9. Severance Biomedical Science Institute, BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. 10. Kidney Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Seoul National University Biomedical Research Institute, Seoul, South Korea. 11. School of Life Science, Handong Global University, Pohang, Gyungbuk, South Korea; Mistle Biotech Co., Ltd., Pohang, Gyungbuk, South Korea. Electronic address: i1948@naver.com.
Abstract
BACKGROUND AND AIM: Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. METHODS AND RESULTS: Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. CONCLUSIONS: The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.
BACKGROUND AND AIM: Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. METHODS AND RESULTS:Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. CONCLUSIONS: The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.
Authors: Sook In Chae; Sang Ah Yi; Ki Hong Nam; Kyoung Jin Park; Jihye Yun; Ki Hyun Kim; Jaecheol Lee; Jeung-Whan Han Journal: Molecules Date: 2020-12-13 Impact factor: 4.411