Regulation by Nicotine of Food Intake and Body Weight: Implications for Obesity Treatment

Obesity is an epidemic problem in the U. S. and many other industrialized nations. Historically, the drugs used for its treatment generally targeted small-molecule neurotransmitters. As research grows to decipher the underlying molecular mechanisms of energy homeostasis, it is becoming evident that the modulating effects of neuropeptides also are critical in the regulation of appetite and metabolism. The search for drugs to modify these monoaminergic and peptidergic pathways may eventually prove successful in the treatment of obesity. While tobacco smoking has long been used as one strategy to maintain a lower body weight, especially by female smokers, its adverse associations with addiction and disease overshadow its potential use as an antiobesity agent. Potential pharmacological effects of nicotine could be better understood as the intricacies of the nicotinic acetylcholine receptor are revealed. The objectives of this review are threefold: (1) to provide an overview of the physiological effects of nicotine on body weight while focusing on the drugs that are available as antiobesity and smoking cessation agents; (2) to describe the status of knowledge of the nicotinic acetylcholine receptor as it relates to energy homeostasis and its potential as an effective treatment modality for obesity; and (3) to present the current knowledge with respect to nicotine's effects on energy homeostatic and reward-related pathways at the molecular level. A better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on body weight will provide insights into potential targets for the development of appropriate medicines for the treatment of obesity.