Autotaxin and Its Product Lysophosphatidic Acid Suppress Brown Adipose Differentiation and Promote Diet-Induced Obesity in Mice
Autotaxin and Its Product Lysophosphatidic Acid Suppress Brown Adipose Differentiation and Promote Diet-Induced Obesity in Mice
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DOI：
10.1210/me.2011-1229
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发表时间：
2012-05-01
影响因子：
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通讯作者：
Smyth, Susan S.
中科院分区：
文献类型：
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作者：
Federico, Lorenzo;Ren, Hongmei;Smyth, Susan S.
棕色脂肪组织是一种生热器官，它将储存的能量以热量的形式释放出来，以保持体温。这一过程也可以防止因饮食导致的肥胖。我们报道，生物活性脂质介体溶血磷脂酸(LPA)显著降低原代培养棕色脂肪细胞前体细胞的分化，而LPA生成酶自体趋化蛋白(ATX)的有效选择性抑制剂促进分化。过量表达ATX的转基因小鼠在喂食高脂饮食时，周边白色脂肪组织中棕色脂肪组织相关基因的表达减少，并且积累的脂肪明显多于野生型对照组。我们的结果表明，ATX及其产物LPA是棕色脂肪脂肪生成的生理相关的负调节因子，并与成熟的外周棕色脂肪组织减少导致小鼠对饮食诱导的肥胖的易感性增加的模型一致。(分子内分泌学26：786-797,2012)
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)