title: Adipose Snail1 Regulates Lipolysis and Lipid Partitioning by Suppressing Adipose Triacylglycerol Lipase Expression.
abstract: Lipolysis provides metabolic fuel; however, aberrant adipose lipolysis results in ectopic lipid accumulation and lipotoxicity. While adipose triacylglycerol lipase (ATGL) catalyzes the first step of lipolysis, its regulation is not fully understood. Here, we demonstrate that adipocyte Snail1 suppresses both ATGL expression and lipolysis. Adipose Snail1 levels are higher in fed mice than in fasted mice and higher in obese mice as opposed to lean mice. Insulin increases Snail1 levels in both murine and human adipocytes, wherein Snail1 binds to the ATGL promoter to repress its expression. Importantly, adipocyte-specific deletion of Snail1 increases adipose ATGL expression and lipolysis, resulting in decreased fat mass and increased liver fat content in mice fed either a normal chow diet or a high-fat diet. Thus, we have identified a Snail1-ATGL axis that regulates adipose lipolysis and fatty acid release, thereby governing lipid partitioning between adipose and non-adipose tissues.
authors.affiliation: School of Life Sciences, University of Northeast Normal University, Changchun 130024, China; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
authors.affiliation: School of Life Sciences, University of Northeast Normal University, Changchun 130024, China. Electronic address: zhouyf383@nenu.edu.cn.
authors.forename: Yifa
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: ruily@umich.edu.
authors.forename: Liangyou
authors.initials: L
authors.lastname: Rui
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000378:metabolism*
chemical_list: D007328:Insulin; D000071250:Snail Family Transcription Factors; D008049:Lipase
keywords: ATGL; NAFLD; Snail1; adipocytes; hepatocytes; insulin resistance; lipolysis; liver steatosis; obesity; type 2 diabetes