Convergence between nicotine and leptin signaling in body weight regulation and obesity

Abstract

Obesity continues to be one of the major epidemic problems in the U. S. and many other industrialized nations. Although treatment strategies historically targeted small-molecule neurotransmitters, more recently it became evident that neuropeptides such as leptin and NPY also play critical roles in the regulation of appetite and metabolism. Discovery of various obesity models in rodents have shed further light on the importance of leptin signaling and modulation of dopaminergic circuitry in determining the mechanisms behind an obese phenotype. While tobacco smoking has long been used as one strategy to control body weight, nicotine’s adverse associations with addiction and disease prohibits its potential use as an approved antiobesity agent. Pharmacological effects of nicotine on energy homeostasis and weight control may stem partly from the emerging convergence between the nicotine- and leptin-driven receptor signaling in regard to the regulation of dopamine in brain and adrenal chromaffin cells. Resolving the intricacies of the diverse set of the nicotinic acetylcholine receptors (nAChR) on which nicotine acts may reveal yet unknown avenues for addiction, obesity, and neurodegenerative research. Moreover, a better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on food intake and body weight will certainly provide novel insights for rapid identification of potential drug targets for the treatment of obesity.