Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT.
Nicotine Tob Res. 2020 Feb 6;22(2):152-163. doi: 10.1093/ntr/ntz010.
Despite health risks associated with smoking, up to 20% of the US population persist in this behavior; many smoke to control body weight or appetite, and fear of post-cessation weight gain can motivate continued smoking. Nicotine and tobacco use is associated with lower body weight, and cessation yields an average weight gain of about 4 kg, which is thought to reflect a return to the body weight of a typical nonsmoker. Nicotine replacement therapies can delay this weight gain but do not prevent it altogether, and the underlying mechanism for how nicotine is able to reduce weight is not fully understood. In rodent models, nicotine reduces weight gain, reduces food consumption, and alters energy expenditure, but these effects vary with duration and route of nicotine administration. Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide and anorexigenic proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Manipulation of nAChR subunit expression within the ARC can block the ability of nicotine and the nicotinic agonist cytisine from decreasing food intake; however, it is unknown exactly how this reduces food intake. This review summarizes the clinical and preclinical work on nicotine, food intake, and weight gain, then explores the feeding circuitry of the ARC and how it is regulated by nicotine. Finally, we propose a novel hypothesis for how nicotine acts on this hypothalamic circuit to reduce food intake. Implications: This review provides a comprehensive and updated summary of the clinical and preclinical work examining nicotine and food intake, as well as a summary of recent work examining feeding circuits of the hypothalamus. Synthesis of these two topics has led to new understanding of how nAChR signaling regulates food intake circuits in the hypothalamus.
尽管吸烟与健康风险相关，但美国仍有 20%的人口持续吸烟；许多人吸烟是为了控制体重或食欲，并且担心戒烟后体重增加会促使他们继续吸烟。尼古丁和烟草的使用与较低的体重有关，而戒烟会导致平均约 4 公斤的体重增加，这被认为反映了恢复到非吸烟者的典型体重。尼古丁替代疗法可以延缓这种体重增加，但并不能完全阻止它，而且尼古丁能够减轻体重的潜在机制尚未完全理解。在啮齿动物模型中，尼古丁可减轻体重增加，减少食物消耗，并改变能量消耗，但这些作用随尼古丁给药的持续时间和途径而变化。尼古丁通过烟碱型乙酰胆碱受体（nAChRs）作用，增加下丘脑弓状核（ARC）中食欲肽和厌食肽前体黑素浓蛋白神经元的发射率。在 ARC 内操纵 nAChR 亚基表达可以阻断尼古丁和烟碱激动剂 cytisine 降低食物摄入的能力；然而，尚不清楚这如何减少食物摄入。这篇综述总结了关于尼古丁、食物摄入和体重增加的临床和临床前工作，然后探讨了 ARC 的进食回路以及尼古丁如何调节它。最后，我们提出了一个关于尼古丁如何作用于这个下丘脑回路以减少食物摄入的新假设。意义：这篇综述提供了关于检查尼古丁和食物摄入的临床和临床前工作的全面和最新总结，以及关于检查下丘脑进食回路的最新工作的总结。这两个主题的综合研究导致了对 nAChR 信号如何调节下丘脑进食回路的新理解。
