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 Mills, Andrew J. Morris, Susan S. Smyth

Research output: Contribution to journalArticle

37 Citations (Scopus)

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
Externally publishedYes

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Brown Adipose Tissue
Obesity
Diet
Brown Adipocytes
Adipogenesis
White Adipose Tissue
High Fat Diet
Body Temperature
Transgenic Mice
Hot Temperature
Fats
Lipids
lysophosphatidic acid
Enzymes
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice. / 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; Morris, Andrew J.; Smyth, Susan S.

In: Molecular Endocrinology, Vol. 26, No. 5, 01.05.2012, p. 786-797.

Research output: Contribution to journalArticle

Federico, L, Ren, H, Mueller, PA, Wu, T, Liu, S, Popovic, J, Blalock, EM, Sunkara, M, Ovaa, H, Albers, HM, Mills, G, Morris, AJ & Smyth, SS 2012, 'Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice', Molecular Endocrinology, vol. 26, no. 5, pp. 786-797. https://doi.org/10.1210/me.2011-1229
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 ; Morris, Andrew J. ; Smyth, Susan S. / Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice. In: Molecular Endocrinology. 2012 ; Vol. 26, No. 5. pp. 786-797.
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