Hu Fang, Xu Yong, Liu Feng
Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China;
Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas; and.
Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E994-E1002. doi: 10.1152/ajpendo.00121.2016. Epub 2016 May 10.
Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes.
哺乳动物雷帕霉素靶蛋白(mTOR)感知营养、能量和激素信号,以调节新陈代谢和能量稳态。下丘脑的mTOR活性与能量状态变化相关,在食物摄入和体重调节中起关键作用。mTOR整合来自多种“能量平衡”激素(如瘦素、胰岛素和胃饥饿素)的信号,尽管其作用会因这些不同的激素刺激以及不同的神经元群体而有所不同。在本综述中,我们总结并强调了关于mTOR复合物1(mTORC1)在下丘脑中的功能作用的最新发现,特别是其在体重、能量消耗和葡萄糖/脂质稳态调节方面的作用。了解大脑中mTOR相关信号传导背后的作用和潜在机制,无疑将为未来对抗肥胖、胰岛素抵抗和糖尿病的治疗和干预开辟新途径。