Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Institute for Zoology, Biocenter, University of Cologne, Cologne, Germany.
Neuron. 2020 Jun 17;106(6):1009-1025.e10. doi: 10.1016/j.neuron.2020.03.022. Epub 2020 Apr 16.
Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOC neurons represent a previously unrecognized GABAergic population of ARC neurons distinct from well-defined feeding regulatory AgRP or POMC neurons. PNOC neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons. Optogenetic activation of PNOC neurons in the ARC and their projections to the bed nucleus of the stria terminalis promotes feeding. Selective ablation of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption. We characterize PNOC neurons as a novel ARC neuron population activated upon palatable food consumption to promote hyperphagia.
高热量饮食会导致过度进食，从而促进肥胖，尽管其潜在机制仍不明确。我们发现，短期高脂肪饮食（HFD）喂养会激活下丘脑弓状核中表达前阿片促黑素细胞皮质素原（PNOC）的神经元。PNOC 神经元代表了之前未被识别的 ARC 神经元中的 GABA 能神经元群，与明确的进食调节 AgRP 或 POMC 神经元不同。PNOC 神经元在 ARC 中密集分支，并向附近的厌食性 POMC 神经元提供抑制性突触输入。光遗传激活 ARC 中的 PNOC 神经元及其投射到终纹床核的纤维会促进进食。选择性消融这些细胞会促进 POMC 神经元在 HFD 暴露时的激活，减少进食，并防止肥胖，但在正常饮食消耗下不会影响食物摄入或体重。我们将 PNOC 神经元描述为一种在摄入美味食物时被激活的新型 ARC 神经元群，以促进过度进食。
