肠道感觉性胃饥饿素信号与脂肪组织交感神经输出之间的相互作用调节代谢稳态。
Crosstalk between Gut Sensory Ghrelin Signaling and Adipose Tissue Sympathetic Outflow Regulates Metabolic Homeostasis.
作者信息
Alex Thomas M, Cui Xin, Artinian Liana R, Cao Qiang, Jing Jia, Silva Felipe C, Wang Shirong, Zigman Jeffrey M, Sun Yuxiang, Shi Hang, Xue Bingzhong
机构信息
Department of Biology, Georgia State University, Atlanta, GA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
出版信息
bioRxiv. 2023 Nov 27:2023.11.25.568689. doi: 10.1101/2023.11.25.568689.
The stomach-derived orexigenic hormone ghrelin is a key regulator of energy homeostasis and metabolism in humans. The ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR), is widely expressed in the brain and gastrointestinal vagal sensory neurons, and neuronal GHSR knockout results in a profoundly beneficial metabolic profile and protects against diet-induced obesity (DIO) and insulin resistance. Here we show that in addition to the well characterized vagal GHSR, GHSR is robustly expressed in gastrointestinal sensory neurons emanating from spinal dorsal root ganglia. Remarkably, sensory neuron GHSR deletion attenuates DIO through increased energy expenditure and sympathetic outflow to adipose tissue independent of food intake. In addition, neuronal viral tract tracing reveals prominent crosstalk between gut non-vagal sensory afferents and adipose sympathetic outflow. Hence, these findings demonstrate a novel gut sensory ghrelin signaling pathway critical for maintaining energy homeostasis.
源自胃的促食欲激素胃饥饿素是人类能量平衡和新陈代谢的关键调节因子。胃饥饿素受体，即生长激素促分泌素受体1a（GHSR），在大脑和胃肠道迷走感觉神经元中广泛表达，神经元GHSR基因敲除会产生非常有益的代谢特征，并预防饮食诱导的肥胖（DIO）和胰岛素抵抗。我们在此表明，除了已得到充分表征的迷走神经GHSR外，GHSR在源自脊髓背根神经节的胃肠道感觉神经元中也大量表达。值得注意的是，感觉神经元GHSR缺失通过增加能量消耗以及独立于食物摄入的向脂肪组织的交感神经输出，减轻了饮食诱导的肥胖。此外，神经元病毒示踪揭示了肠道非迷走感觉传入神经与脂肪交感神经输出之间存在显著的串扰。因此，这些发现证明了一种对维持能量平衡至关重要的新型肠道感觉胃饥饿素信号通路。
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