Cell type transcriptomics of hypothalamic energy-sensing neuron responses to fasting

AGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Examination of 2 different neuronal cell types under 2 conditions.刺鼠相关肽（AGRP）神经元是一类下丘脑神经元群体，能够感知生理性能量缺乏状态并进而增强食欲。用于能量感知以及神经元输出上调的分子与细胞过程，对于理解中枢神经系统对能量缺乏状态（例如减重期间）的应答机制至关重要。细胞类型特异性转录组学可用于鉴定能够对抗体重减轻的通路，但在成年小鼠中，此类研究受限于诸多技术难题。本研究报道了正常饱食及能量缺乏状态下AGRP神经元的高质量基因表达谱。为便于对照分析，本研究同时检测了阿黑皮素原（POMC）神经元——一类与AGRP神经元交错分布且可抑制食欲的神经元群体。本数据集首次鉴定出信号通路、离子通道、神经肽以及G蛋白偶联受体的细胞类型选择性参与特征。结合针对这些通路的验证与操控方法，本数据集极大拓展了神经元调控体重的分子认知，或可为开发肥胖症与进食障碍的治疗策略提供重要参考。本研究在两种实验条件下对两类不同的神经元细胞类型展开了检测分析。