Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Cell Metab. 2019 Jul 2;30(1):111-128.e6. doi: 10.1016/j.cmet.2019.04.001. Epub 2019 Apr 25.
Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie-dense food; NPY neurons in the central amygdala are responsible for an exacerbated response to a combined stress and high-fat-diet intervention. Central amygdala NPY neuron-specific Npy overexpression mimics the obese phenotype seen in a combined stress and high-fat-diet model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure as readouts, we demonstrate that selective activation of central amygdala NPY neurons results in increased food intake and decreased energy expenditure. Mechanistically, it is the diminished insulin signaling capacity on central amygdala NPY neurons under combined stress and high-fat-diet conditions that leads to the exaggerated development of obesity.
神经肽 Y（NPY）在下丘脑发挥强大的食欲刺激作用。然而，下丘脑外核也产生 NPY，但它对能量平衡的影响尚不清楚。在这里，我们揭示了一条以前未知的进食刺激途径，它在应激与高热量食物结合的情况下被激活；杏仁中央核中的 NPY 神经元负责对联合应激和高脂肪饮食干预产生加剧的反应。杏仁中央核 NPY 神经元特异性 Npy 过表达模拟了联合应激和高脂肪饮食模型中观察到的肥胖表型，而选择性消融 Npy 可预防这种表型。我们使用食物摄入量和能量消耗作为读出值，证明选择性激活杏仁中央核 NPY 神经元会导致食物摄入量增加和能量消耗减少。从机制上讲，正是联合应激和高脂肪饮食条件下杏仁中央核 NPY 神经元的胰岛素信号转导能力减弱导致肥胖的过度发展。
