Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake

Abstract

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.

Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits

“…injection of EtOH (n = 9/group, two-way repeated-measures ANOVA, p = ns). Data are expressed as mean ± SEM, ns p > 0.05. both AgRP and POMC neurons that are potently activated by drugs of abuse, as is the case for nicotine (Calarco et al, 2018;Calarco and Picciotto, 2019). This dysregulation of hypothalamic neuron activity further supports the notion that nutrients and drugs utilize distinct pathways and may in part contribute to the detrimental effects of drugs on the brain and behavior.…”

The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice

“…However, the body weight loss was not reduced in JPYFII treated CS + IAV mice compared to sham + MEM mice. As reported, nicotine in CS has a great effect on appetite suppression [54]. Thus, the data demonstrated that JPYFII formulation suppressed the inflammation in lungs of CS+IAV mice but did not alleviate the suppression of appetite by nicotine.…”

Mechanisms of Nicotine Addiction

“…Recent studies show that both POMC and NPY neurons express almost all nAChR subunits and that deletion of the β4 nAChR subunit from either subtype is sufficient to attenuate nicotinic-induced decreases in food intake (Calarco et al 2018). Interestingly, in a slice preparation, the effects of nicotine on firing of POMC neurons persist longer than firing of NPY neurons (Parikh et al 2007(Parikh et al , 2008, showing that at the circuit level, stimulation of nAChRs shifts the balance toward neuronal patterns that signal satiety (Calarco and Picciotto 2020).…”