Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
EMBO Rep. 2012 Mar 1;13(3):258-65. doi: 10.1038/embor.2011.260.
Autophagy degrades cytoplasmic contents to achieve cellular homeostasis. We show that selective loss of autophagy in hypothalamic proopiomelanocortin (POMC) neurons decreases α-melanocyte-stimulating hormone (MSH) levels, promoting adiposity, impairing lipolysis and altering glucose homeostasis. Ageing reduces hypothalamic autophagy and α-MSH levels, and aged-mice phenocopy, the adiposity and lipolytic defect observed in POMC neuron autophagy-null mice. Intraperitoneal isoproterenol restores lipolysis in both models, demonstrating normal adipocyte catecholamine responsiveness. We propose that an unconventional, autophagosome-mediated form of secretion in POMC neurons controls energy balance by regulating α-MSH production. Modulating hypothalamic autophagy might have implications for preventing obesity and metabolic syndrome of ageing.
自噬可降解细胞质内容物以实现细胞内稳态。我们发现，选择性敲除下丘脑 proopiomelanocortin (POMC) 神经元中的自噬会降低 α-促黑素细胞激素 (MSH) 水平，从而促进肥胖，损害脂肪分解并改变葡萄糖稳态。衰老会降低下丘脑的自噬和 α-MSH 水平，而衰老的小鼠则表现出 POMC 神经元自噬缺失小鼠中观察到的肥胖和脂肪分解缺陷的表型。腹腔内异丙肾上腺素可恢复两种模型中的脂肪分解，表明脂肪细胞儿茶酚胺反应正常。我们提出，POMC 神经元中一种非传统的、自噬体介导的分泌形式通过调节 α-MSH 的产生来控制能量平衡。调节下丘脑自噬可能对预防肥胖和衰老相关的代谢综合征具有重要意义。
