Minireview: Central Sirt1 regulates energy balance via the melanocortin system and alternate pathways.
Minireview: Central Sirt1 regulates energy balance via the melanocortin system and alternate pathways.
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DOI：
10.1210/me.2014-1115
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发表时间：
2014-06
影响因子：
--
通讯作者：
Anika M Toorie;E. Nillni
中科院分区：
文献类型：
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作者：
Anika M Toorie;E. Nillni
在发达国家，尽管有许多治疗策略可用，肥胖症及其相关的合并症仍然盛行。越来越多的证据表明，来自外周和大脑内部的多种输入共同作用，以恒定的速度维持能量新陈代谢。在中央层面，下丘脑是神经系统的主要组成部分，解释肥胖或与营养相关的输入；它提供荷尔蒙和行为反应，最终目的是调节能量摄入和能量消耗。在分子水平上，被称为营养能量传感器的酶调节那些参与能量平衡的组织的代谢反应(1)。两个关键的能量/营养传感器，哺乳动物的雷帕霉素靶标和AMP激活的激酶，参与控制下丘脑和周围组织的食物摄入量(2，3)。第三个最新发现的营养传感器是Sirt1(Sirt1)，它是一种依赖于烟酰胺腺嘌呤二核苷酸的脱乙酰酶，具有维持全身能量平衡的功能。一些研究已经强调了外周和中枢Sirt1在调节身体新陈代谢中的作用，但其核心作用仍然存在激烈的争论。由于中枢Sirt1的不透明，S在能量平衡中的作用是其细胞特有的功能。由于其强大的中枢表达，靶向Sirt1信号的细胞特异性下游介质可能有助于对抗肥胖。然而，在生理相关模型的背景下，有令人信服的证据表明，中枢Sirt1抑制本身足以促进瘦肉型和节食型肥胖状态的能量负平衡。
In developed nations, the prevalence of obesity and its associated comorbidities continue to prevail despite the availability of numerous treatment strategies. Accumulating evidence suggests that multiple inputs from the periphery and within the brain act in concert to maintain energy metabolism at a constant rate. At the central level, the hypothalamus is the primary component of the nervous system that interprets adiposity or nutrient-related inputs; it delivers hormonal and behavioral responses with the ultimate purpose of regulating energy intake and energy consumption. At the molecular level, enzymes called nutrient energy sensors mediate metabolic responses of those tissues involved in energy balance ( 1 ). Two key energy/nutrient sensors, mammalian target of rapamycin and AMP-activated kinase, are involved in the control of food intake in the hypothalamus as well as in peripheral tissues ( 2 , 3 ). The third more recently discovered nutrient sensor, Sirtuin1 (Sirt1), a nicotinamide adenine dinucleotide-dependent deacetylase, functions to maintain whole-body energy homeostasis. Several studies have highlighted a role for both peripheral and central Sirt1 in regulating body metabolism, but its central role is still heavily debated. Owing to the opaqueness of central Sirt1's role in energy balance are its cell-specific functions. Because of its robust central expression, targeting cell-specific downstream mediators of Sirt1 signaling may help to combat obesity. However, when placed in the context of a physiologically relevant model, there is compelling evidence that central Sirt1 inhibition in itself is sufficient to promote negative energy balance in both the lean and diet-induced obese state.