来自密歇根大学的华裔科学家管坤良教授在最新一期的Cell Metabolism上发表mTOR信号转导活性与机体能量平衡的最新研究进展，文章标题：Critical Role for Hypothalamic mTOR Activity in Energy Balance。
mTOR（mammalian target of rapamycin）是一种非典型的丝氨酸/苏氨酸蛋白激酶，它是调节细胞存活、增殖和血管生成的信号转导途径中的重要调控蛋白。之前，mTOR一直被作为免疫抑制药物雷帕霉素的靶标进行研究。
肿瘤抑制因子TSC1和TSC2是mTOR信号通路上游的重要抑制调节器。研究小组构建了一个模型小鼠，使其缺失Rip2/Cre介导的Tsc1（Rip-Tsc1cKO mice），结果发现模型小鼠发生一系列的代谢变化，摄取过量的食物导致肥胖症，这些研究结果表明下丘脑的Tsc1缺失会导致mTOR信号通路的反馈系统失控。
研究结果表明，mTOR信号会影响Pomc神经元，过度活跃的mTOR信号会阻断机体的代谢异化功能，加上过度的摄取营养导致生物体产生肥胖症。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell Metabolism,8 April 2009 doi:10.1016/j.cmet.2009.03.005
Critical Role for Hypothalamic mTOR Activity in Energy Balance
Hiroyuki Mori1,2,Ken Inoki1,2,Heike Münzberg3,9,Darren Opland3,4,Miro Faouzi3,Eneida C. Villanueva2,3,Tsuneo Ikenoue1,David Kwiatkowski7,Ormond A. MacDougald2,3,Martin G. Myers2,3,4,,andKun-Liang Guan1,5,6,8,,
1 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
2 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
3 Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA
4 Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA
5 Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
6 Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109, USA
7 Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA
8 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0815, USA
9 Present address: Pennington Biological Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
The mammalian target of rapamycin (mTOR) promotes anabolic cellular processes in response to growth factors and metabolic cues. The TSC1 and TSC2 tumor suppressors are major upstream inhibitory regulators of mTOR signaling. Mice with Rip2/Cre-mediated deletion of Tsc1 (Rip-Tsc1cKO mice) developed hyperphagia and obesity, suggesting that hypothalamic disruption (for which Rip2/Cre is well known) of Tsc1 may dysregulate feeding circuits via mTOR activation. Indeed, Rip-Tsc1cKO mice displayed increased mTOR signaling and enlarged neuron cell size in a number of hypothalamic populations, including Pomc neurons. Furthermore, Tsc1 deletion with Pomc/Cre (Pomc-Tsc1cKO mice) resulted in dysregulation of Pomc neurons and hyperphagic obesity. Treatment with the mTOR inhibitor, rapamycin, ameliorated the hyperphagia, obesity, and the altered Pomc neuronal morphology in developing or adult Pomc-Tsc1cKO mice, and cessation oftreatment reinstated these phenotypes. Thus, ongoing mTOR activation in Pomc neurons blocks the catabolic function of these neurons to promote nutrient intake and increased adiposity.
