The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Nat Commun. 2017 Jan 10;8:14014. doi: 10.1038/ncomms14014.
Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain's feeding circuits-the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger-display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices. Furthermore, by circuit-specific chemogenetic interference in vivo, we find that the Agrp cell activity is essential for ethanol-induced overeating in the absence of societal factors, in single-housed mice. These data reveal how a widely consumed nutrient can paradoxically sustain brain starvation signals, and identify a biological factor required for appetite evoked by alcohol.
饮酒与人类暴食有关。这种暴食是一个临床关注的问题，但它的原因令人费解，因为酒精（乙醇）是一种高热量的营养物质，而卡路里的摄入通常会抑制大脑的食欲信号。乙醇引起暴食的生物学因素尚不清楚，有人提出了一些社会因素。在这里，我们发现大脑进食回路的核心要素——下丘脑 Agrp 神经元，通常在饥饿时被激活，并引发强烈的饥饿感——在脑切片中暴露于膳食剂量的乙醇时会表现出电和生化过度活跃。此外，通过体内特定于回路的化学遗传干扰，我们发现 Agrp 细胞活性对于在没有社会因素的情况下，单笼饲养的小鼠由酒精引起的暴食是必需的。这些数据揭示了一种广泛消费的营养物质如何能反常地维持大脑饥饿信号，并确定了由酒精引起的食欲所需的生物学因素。
