How Leptin Controls the Drive to Eat

Central regulation of energy homeostasis The amount of energy consumed relative to that expended by an animal dictates the expansion or contraction of its body energy (fat) stores, which are crucial for survival during extended periods without feeding. Body mass and adiposity generally remain within a narrow range over the long term, consistent with the homeostatic control of body adiposity. Indeed, in humans and other animals, insufficient caloric intake to match utilization (which decreases fat stores) promotes hunger and decreases energy expenditure to promote the restoration of adiposity to previous levels: This response to decreased energy stores underlies the eventual weight regain experienced by the vast majority of overweight individuals who initially lose weight (by dieting). Conversely, overfeeding (e.g., by the direct infusion of food into the gut in experimental animals) suppresses voluntary food intake and increases energy expenditure, reducing energy stores toward baseline. Thus, animals possess homeostatic systems that modulate feeding and energy utilization to maintain adiposity within acceptable levels. Obesity, then, must result from overriding the processes that control energy homeostasis. In animals, the central nervous system (CNS) detects fuel availability and coordinates physiologic and behavioral parameters to maintain long-term energy balance. This homeostatic regulation of energy balance is initiated by specialized neurons in the brainstem and hypothalamus that sense relevant cues, such as fuels and hormones that reflect nutritional status. To control feeding, these neurons modulate two essentially separate parameterssatiation and the incentive to eat. Generally speaking, satiation (which is commonly associated with a feeling of fullness) results from the action of interconnected neural circuits in the brainstem and hypothalamus that promote meal termination. Dopamine (DA)containing midbrain neurons that project to limbic regions (the mesolimbic DA (MLDA) system) encode the attractiveness food, as well as other rewards (sex, drugs of How Leptin Controls the Drive to Eat Christa M. Patterson, Martin G. Myers, Jr* Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA