Nicotine targets in systems regulating energy homeostasis will be subdivided into peripheral input and output structures, and central integrative structures (Figures 1 and and2).2). With respect to central structures, moreover we will discuss how nicotine affects homeostatic and reward circuits that regulate feeding and energy metabolism, as well as their interactions. Drug dependence is known to involve appetitive mechanisms, and the effects of nicotine on body weight, eating, and obesity are therefore likely to contribute to nicotine addiction. Starting from pioneering studies in the 1970s and early 1980s (Falkeborn, Larsson, & Nordberg, 1981; Grunberg, 1982; Grunberg, Bowen, Maycock, & Nespor, 1985; McNair & Bryson, 1983; Schechter & Cook, 1976; Wack & Rodin, 1982), multiple effects of nicotine and smoking on food consumption, energy expenditure, as well as food hedonics have been identified.

In this review, we will outline the cellular and molecular mechanisms that may underlie the effects of nicotine on energy intake, expenditure, and hedonics of food consumption. Figure 1. Schematic representation of the principal structures of the systems that regulate energy metabolism. AMY = amygdala; ARC = arcuate nucleus; DMH = dorsomedial hypothalamic nucleus; GI = gastrointestinal; INS = insula; LH = lateral hypothalamus; nAc = nucleus … Figure 2. Expression of nicotinic acetylcholine receptors in systems that regulate energy metabolism. For abbreviations, see legend to figure 1. ANS = autonomic nervous system; BAT = brown adipose tissue; ENS = enteric nervous system; WAT = white adipose tissue.

… Effects of Nicotine on Body Weight and Metabolism Due to the almost ubiquitous expression of nAChRs in central and peripheral neuronal cells and nonneuronal cells in peripheral organs that are involved in the regulation of body weight, nicotine has potentially complex actions on energy homeostasis. Thus, the impact of systemic nicotine may be different depending on food quality and availability, behavioral or metabolic states as well as individual genetics, personality, and habits. Moreover, it is well known that nicotine has an inverted U dose-response relationship on its receptors and in its behavioral actions, and it desensitizes as well as upregulates its receptors upon prolonged administration. Therefore, nicotine dose and modality of administration (e.

g., acute, chronic repeated, or chronic continuous administration, Brefeldin_A passive, or active administration) may lead to markedly different effects. Finally, it must be kept in mind that averaged data from laboratory, often inbred, animals kept in impoverished environmental conditions and eating lab chow food underestimate the varieties of impacts that nicotine may exert in animals living in natural environments and humans. In general terms, energy homeostasis can be regulated by intervening at the level of food (i.e., energy) intake and/or on energy expenditure.