title: Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway.
abstract: Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha-lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP-activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP-activated protein kinase pathway, the translocation of sterol regulatory element-binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2.
authors.affiliation: Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China. Electronic address: yangyi73422@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Central Lab. Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021, China. Electronic address: jjzhao@medmail.com.cn.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D008063:Thioctic Acid; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Alpha-lipoic acid; FoxO1; Nonalcoholic fatty liver disease; Nrf2; SIRT1; SREBP-1