Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice |
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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 |
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Institution: | Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky 40536, USA. |
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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 diet-induced obesity in mice. |
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