title: Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice.
abstract: Brown adipose tissue is a thermogenic organ that dissipates stored energy as heat to maintain body temperature. This process may also provide protection from development of diet-induced obesity. We report that the bioactive lipid mediator lysophosphatidic acid (LPA) markedly decreases differentiation of cultured primary brown adipocyte precursors, whereas potent selective inhibitors of the LPA-generating enzyme autotaxin (ATX) promote differentiation. Transgenic mice overexpressing ATX exhibit reduced expression of brown adipose tissue-related genes in peripheral white adipose tissue and accumulate significantly more fat than wild-type controls when fed a high-fat diet. Our results indicate that ATX and its product LPA are physiologically relevant negative regulators of brown fat adipogenesis and are consistent with a model in which a decrease in mature peripheral brown adipose tissue results in increased susceptibility to diet-induced obesity in mice.
authors.affiliation: Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Federico
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Paul A
authors.initials: PA
authors.lastname: Mueller
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Jelena
authors.initials: J
authors.lastname: Popovic
authors.forename: Eric M
authors.initials: EM
authors.lastname: Blalock
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Huib
authors.initials: H
authors.lastname: Ovaa
authors.forename: Harald M
authors.initials: HM
authors.lastname: Albers
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D054392:Adipokines / Q000097:blood; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071256:Uncoupling Protein 1; D000099189:Lysophospholipase D
chemical_list: D054392:Adipokines; D016207:Cytokines; D004791:Enzyme Inhibitors; D007473:Ion Channels; D008246:Lysophospholipids; D024101:Mitochondrial Proteins; D010727:Phosphoric Diester Hydrolases; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000071256:Uncoupling Protein 1; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid