Weiqiang Chen1,2, Xiaoli Zhang1, Minwen Xu3, Lixia Jiang3, Min Zhou4, Wenjun Liu4, Zhijun Chen4, Yucai Wang5, Qingyan Zou5, Liefeng Wang6. 1. Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular DiseasesMinistry of Education, Gannan Medical University, Ganzhou, 341000, China. 2. KingMed Diagnostics, Guangzhou, 510320, China. 3. First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China. 4. Undergraduate of Biotechnology, Gannan Medical University, Ganzhou, 341000, China. 5. Jiangxi Xi Di Biological Science and Technology Co., Ltd., Ganzhou, 341000, China. 6. Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular DiseasesMinistry of Education, Gannan Medical University, Ganzhou, 341000, China. 469730795@qq.com.
Abstract
PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of chronic liver disease in developing countries. The pathogenesis is complex, and there is currently no effective treatment. Betaine is an essential intermediate in choline catabolism and an important component of the methionine cycle. Betaine deficiency is associated with NAFLD severity, and its mechanism needs to be further elaborated. METHODS: In this study, an NAFLD mouse model was established by feeding ApoE-/- mice a high-fat diet. The effects of betaine on NAFLD were investigated, including its mechanism. RESULTS: In this study, after treatment with betaine, blood lipid levels and liver damage were significantly decreased in the NAFLD mouse model. The fat infiltration of the liver tissues of high-fat diet (HFD)-fed mice after betaine administration was significantly improved. Betaine treatment significantly upregulated AMP-activated protein kinase (AMPK), fibroblast growth factor 10 (FGF10), and adipose triglyceride lipase (ATGL) protein levels both in vivo and in vitro and suppressed lipid metabolism-related genes. Furthermore, the overexpression of FGF10 increased the protein level of AMPK and decreased lipid accumulation in HepG2 cells. CONCLUSION: Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE-/- mice.
PURPOSE:Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of chronic liver disease in developing countries. The pathogenesis is complex, and there is currently no effective treatment. Betaine is an essential intermediate in choline catabolism and an important component of the methionine cycle. Betaine deficiency is associated with NAFLD severity, and its mechanism needs to be further elaborated. METHODS: In this study, an NAFLD mouse model was established by feeding ApoE-/- mice a high-fat diet. The effects of betaine on NAFLD were investigated, including its mechanism. RESULTS: In this study, after treatment with betaine, blood lipid levels and liver damage were significantly decreased in the NAFLD mouse model. The fat infiltration of the liver tissues of high-fat diet (HFD)-fed mice after betaine administration was significantly improved. Betaine treatment significantly upregulated AMP-activated protein kinase (AMPK), fibroblast growth factor 10 (FGF10), and adipose triglyceride lipase (ATGL) protein levels both in vivo and in vitro and suppressed lipid metabolism-related genes. Furthermore, the overexpression of FGF10 increased the protein level of AMPK and decreased lipid accumulation in HepG2 cells. CONCLUSION: Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE-/- mice.
Authors: Ganga Karunamuni; Megan M Sheehan; Yong Qiu Doughman; Shi Gu; Jiayang Sun; Youjun Li; James P Strainic; Andrew M Rollins; Michael W Jenkins; Michiko Watanabe Journal: Alcohol Clin Exp Res Date: 2017-10-11 Impact factor: 3.455
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