來(lái)自密歇根大學(xué)的華裔科學(xué)家管坤良教授在最新一期的Cell Metabolism上發(fā)表mTOR信號(hào)轉(zhuǎn)導(dǎo)活性與機(jī)體能量平衡的最新研究進(jìn)展,，文章標(biāo)題：Critical Role for Hypothalamic mTOR Activity in Energy Balance,。
mTOR（mammalian target of rapamycin）是一種非典型的絲氨酸/蘇氨酸蛋白激酶，它是調(diào)節(jié)細(xì)胞存活,、增殖和血管生成的信號(hào)轉(zhuǎn)導(dǎo)途徑中的重要調(diào)控蛋白,。之前，mTOR一直被作為免疫抑制藥物雷帕霉素的靶標(biāo)進(jìn)行研究,。
腫瘤抑制因子TSC1和TSC2是mTOR信號(hào)通路上游的重要抑制調(diào)節(jié)器,。研究小組構(gòu)建了一個(gè)模型小鼠，使其缺失Rip2/Cre介導(dǎo)的Tsc1（Rip-Tsc1cKO mice）,，結(jié)果發(fā)現(xiàn)模型小鼠發(fā)生一系列的代謝變化,，攝取過(guò)量的食物導(dǎo)致肥胖癥，這些研究結(jié)果表明下丘腦的Tsc1缺失會(huì)導(dǎo)致mTOR信號(hào)通路的反饋系統(tǒng)失控,。
研究結(jié)果表明,，mTOR信號(hào)會(huì)影響Pomc神經(jīng)元，過(guò)度活躍的mTOR信號(hào)會(huì)阻斷機(jī)體的代謝異化功能,，加上過(guò)度的攝取營(yíng)養(yǎng)導(dǎo)致生物體產(chǎn)生肥胖癥,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
