Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice

Lorenzo Federico, Hongmei Ren, Paul A. Mueller, Tao Wu, Shuying Liu, Jelena Popovic, Eric M. Blalock, Manjula Sunkara, Huib Ovaa, Harald M. Albers, Gordon B. Mills, Andrew J. Morris, Susan S. Smyth

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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 dietinduced obesity in mice.

Original languageEnglish (US)
Pages (from-to)786-797
Number of pages12
JournalMolecular Endocrinology
Volume26
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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