Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons

The hypothalamic arcuate nucleus (ARC) contains two main populations of neurons essential for energy homeostasis: neuropeptide Y (NPY) neurons, which are orexigenic and stimulate food intake, and proopiomelanocortin (POMC) neurons, which have an anorexigenic effect. Located near the blood-brain barrier, ARC neurons sense blood-borne signals such as leptin, insulin, and glucose. Exogenous substances, such as nicotine, can also alter ARC neuron activity and energy balance. Nicotine, an addictive drug used worldwide, inhibits appetite, and reduces body weight, although its mechanisms in regulating ARC neurons are not well understood. Using electrophysiological techniques in brain slices, we investigated the effects of nicotine on POMC and NPY neurons at physiological glucose concentrations. We found that nicotine increased the firing rate of POMC and inhibited NPY neurons. Additionally, nicotine-enhanced glutamatergic inputs to POMC cells and GABAergic inputs to NPY neurons, mediated by α7 and α4β2 nicotinic acetylcholine receptors (nAChRs), respectively. These findings can contribute to the understanding of the anorexigenic effects of nicotine in smokers. [Display omitted] •Nicotine increases the activity of proopiomelanocortin (POMC) neurons in a long-lasting way.•Nicotine inhibits the activity of neuropeptide Y neurons (NPY).•Modulation of the glutamatergic input to POMC neurons is mediated through α7 nAChRs.•Modulation of the GABAergic input to the NPY neurons is mediated through α4β2 nAChRs.