2012年9月28日 电 /生物谷BIOON/ --近日,Dana-Farber癌症研究所科学家证实翻转在白色脂肪细胞中新发现的一种分子开关,可以使老鼠即使在吃高热量的饮食情况下也不会变得肥胖或导致脂肪细胞发生炎症反应。
相关研究结果将刊登在9月28日的Cell杂志上,该研究发现了一个能将生热作用(燃烧卡路里产生热量)和脂肪细胞中炎症的发展联系起来的分子。这两个过程先前被认为是独立的。生热作用在代谢和保持健康体重中起着重要的作用,而炎症触发胰岛素抵抗引发糖尿病。研究人员Bruce Spiegelman博士等发现这个开关分子TRPV4蛋白质在存储多余热量的白色脂肪细胞中是高表达的。
在这项研究中,研究人员培育出缺乏TRPV4的小鼠。在TRPV4不存在的情况下,白细胞打开开启一组基因,消耗能量以产生热量,而不是存储能量成为多余的脂肪。这种“生热”过程通常发生在小动物和人类婴儿应对寒冷环境时的棕色或米色脂肪中。
TRPV4缺陷小鼠被给予一个高热量饮食好几个星期,但这些小鼠并没有变得肥胖,自身脂肪细胞炎症和胰岛素抵抗的水平反而降低了。Spiegelman说:我们已经确定了上述现象的具体调控蛋白,当该蛋白被抑制时可激活米色脂肪组织,抑制炎症反应TRPV4的角色是调节脂肪细胞的生热作用和炎性反应,因此为治疗肥胖及相关代谢性疾病提供了一个潜在靶点。(生物谷Bioon.com)
doi:10.1016/j.cell.2012.08.034
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TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis
Li Ye, Sandra Kleiner, Jun Wu, Rajan Sah, Rana K. Gupta, Alexander S. Banks, Paul Cohen, Melin J. Khandekar, Pontus Bostr?m, Rina J. Mepani, Dina Laznik, Theodore M. Kamenecka, Xinyi Song, Wolfgang Liedtke, Vamsi K. Mootha, Pere Puigserver, Patrick R. Griffin, David E. Clapham, Bruce M. Spiegelman
PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases.