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 journalArticle

    45 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 1 2012

    ASJC Scopus subject areas

    • Molecular Biology
    • Endocrinology

    Fingerprint Dive into the research topics of 'Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice'. Together they form a unique fingerprint.

  • Cite this

    Federico, L., Ren, H., Mueller, P. A., Wu, T., Liu, S., Popovic, J., Blalock, E. M., Sunkara, M., Ovaa, H., Albers, H. M., Mills, G. B., Morris, A. J., & Smyth, S. S. (2012). Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice. Molecular Endocrinology, 26(5), 786-797. https://doi.org/10.1210/me.2011-1229