Journal
MOLECULAR ENDOCRINOLOGY
Volume 26, Issue 5, Pages 786-797Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2011-1229
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Funding
- NIH [HL078663, GM050388, 1P20RR021954, UL1RR033173]
- American Heart Association
- Veterans Affairs Merit Award
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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. (Molecular Endocrinology 26: 786-797, 2012)
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