The electrophysiology of feeding circuits.

Obesity is quickly becoming one of the most common and debilitating disorders of the developed world. More than 60% of American adults are now overweight or obese, predisposing them to a host of chronic diseases. To understand the etiology of obesity, and to discover new therapies for obesity, we must understand the components of energy balance. In simple terms, energy intake (feeding) must equal energy expenditure (physical activity, basal metabolism and adaptive thermogenesis) for body weight homeostasis. To maintain homeostasis, neurocircuitry must sense both immediate nutritional status and the amount of energy stored in adipose tissue, and must be able to provide appropriate output to balance energy intake and energy expenditure. The brain receives various signals that carry information about nutritional and metabolic status including neuropeptide PYY(3-36), ghrelin, cholecystokinin, leptin, glucose and insulin. Circulating satiety signals access the brain either by "leakage" across circumventricular organs or transport across the blood-brain barrier. Signals can also activate sensory vagal terminals that innervate the whole gastrointestinal tract.