Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de Novo Recruitment of Brown Adipocytes
Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de Novo Recruitment of Brown Adipocytes
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DOI：
10.1126/science.1186034
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发表时间：
2010-05-28
期刊：
影响因子：
56.9
通讯作者：
Herzig, Stephan
中科院分区：
文献类型：
--
作者：
Vegiopoulos, Alexandros;Mueller-Decker, Karin;Herzig, Stephan
肥胖是由慢性能量过剩和白色脂肪组织（WAT）中过量脂质储存引起的。相比之下，棕色脂肪组织（BAT）通过适应性产热有效地燃烧脂质。研究小鼠模型，我们表明，环氧合酶（考克斯）-2，前列腺素（PG）合成的限速酶，是一个下游效应的β-肾上腺素能信号在WAT和所需的诱导BAT在WAT仓库。PG使确定的间充质祖细胞向棕色脂肪细胞表型分化。WAT中考克斯-2的过表达诱导WAT中BAT的重新募集，增加全身能量消耗，并保护小鼠免受高脂饮食诱导的肥胖。因此，考克斯-2似乎是BAT重新募集的组成部分，这表明PG途径调节全身能量稳态。
Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)-2, a rate-limiting enzyme in prostaglandin (PG) synthesis, is a downstream effector of beta-adrenergic signaling in WAT and is required for the induction of BAT in WAT depots. PG shifted the differentiation of defined mesenchymal progenitors toward a brown adipocyte phenotype. Overexpression of COX-2 in WAT induced de novo BAT recruitment in WAT, increased systemic energy expenditure, and protected mice against high-fat diet-induced obesity. Thus, COX-2 appears integral to de novo BAT recruitment, which suggests that the PG pathway regulates systemic energy homeostasis.