Autotaxin and Its Product Lysophosphatidic Acid Suppress Brown Adipose Differentiation and Promote Diet-Induced Obesity in Mice

作者：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^*

来源：Molecular Endocrinology, 2012, 26(5): 786-797.

DOI：10.1210/me.2011-1229

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)

• 出版日期2012-5