Investigation into the role of hypothalamic SIRT1 in regulating energy metabolism.

SIRT1将外周器官的能量可获得性状态与细胞代谢联系起来。胰岛素和瘦素信号调节下丘脑弓状核的摄食。据报道，SIRT1在体外可以改善胰岛素敏感性，但下丘脑Sirt1在调节摄食方面的作用尚未得到解决。我们发现下丘脑Sirt1蛋白水平和稳定性受食物摄入量的调节。强迫野生型Sirt1在下丘脑内侧基底核表达，通过抑制促食欲素神经肽AgRP的表达，抑制了过度吞噬和体重增加。

Sirt1 links the energy availability status with cellular metabolism in peripheral organs. Insulin and leptin signaling regulate food intake in the arcuate nucleus of the hypothalamus. Sirt1 has been reported to improve insulin sensitivity in vitro, but the role of hypothalamic Sirt1 in regulating feeding has not been addressed. We found that hypothalamic Sirt1 protein level and stability is regulated by food intake. Forced expression of wild-type Sirt1 in the mediobasal hypothalamus suppressed hyperphagia and weight gain by suppressing the expression of the orexigenic neuropeptide AgRP.