Autotaxin and Its Product Lysophosphatidic Acid Suppress Brown Adipose Differentiation and Promote Diet-Induced Obesity in Mice

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 differentiatio...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2012-05, Vol.26 (5), p.786-797
Main Authors: Federico, Lorenzo, Ren, Hongmei, Mueller, Paul A, Wu, Tao, Liu, Shuying, Popovic, Jelena, Blalock, Eric M, Sunkara, Manjula, Ovaa, Huib, Albers, Harald M, Mills, Gordon B, Morris, Andrew J, Smyth, Susan S
Format: Article
Language:English
Subjects:
Adipogenesis - drug effects
Adipokines - blood
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - immunology
Adipose Tissue, Brown - metabolism
Adipose Tissue, Brown - pathology
Animals
Cells, Cultured
Cytokines - blood
Diet, High-Fat - adverse effects
Embryo, Mammalian
Enzyme Inhibitors - pharmacology
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - pathology
Gene Expression Regulation - drug effects
Ion Channels - genetics
Ion Channels - metabolism
Lysophospholipids - metabolism
Male
Mice
Mice, Transgenic
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Obesity - etiology
Obesity - immunology
Obesity - metabolism
Obesity - pathology
Original Research
Phosphoric Diester Hydrolases - chemistry
Phosphoric Diester Hydrolases - genetics
Phosphoric Diester Hydrolases - metabolism
Random Allocation
Recombinant Proteins - antagonists & inhibitors
Recombinant Proteins - metabolism
RNA, Messenger - metabolism
Subcutaneous Fat - drug effects
Subcutaneous Fat - immunology
Subcutaneous Fat - metabolism
Subcutaneous Fat - pathology
Uncoupling Protein 1
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Description
Summary: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.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2011-1229