The neurobiology of eating disorders

Peptide systems in the brain have a profound impact on behavioral and physiological systems related to eating behavior, nutrient partitioning, and body weight gain. The activity of these peptide systems is controlled by specific physiological signals and shifts dramatically in relation to biological rhythms and nutritional changes. This presentation will focus on two peptide systems, neuropeptide Y (NPY) and galanin (GAL). These systems both produce hyperphagia and reduce energy expenditure; however, they have distinct actions, they involve different neurocircuits, and they are differentially activated in relation to particular physiological and pathological states. The actions of NPY are focused on processes that enhance carbohydrate intake and metabolism, designed to restore positive energy balance at times of increased energy demand or carbohydrate depletion. This peptide operates through a specific hypothalamic circuit, involving NPY-synthesizing cell bodies of the arcuate nucleus (ARC) and NPY projections to the medial paraventricular nucleus (PVN). It is highly responsive to the stimulatory actions of corticosterone (CORT) on gene expression and inhibited by signals associated with increased glucose uptake or utilization. This neurocircuit is most strongly activated at the start of the active feeding cycle or early in development, before puberty. At these times, carbohydrate intake is high, dietary fat is low, and the body is most prepared to metabolize carbohydrate. Neuropeptide Y is also activated by periods of food restriction. In distinct contrast, GAL acts to stimulate the ingestion of fat while reducing energy expenditure. It operates through neurons in the PVN and medial preoptic area (MPO), which project locally as well as to the median eminence. While this GAL neurocircuit is insensitive to CORT and to changes in glucose utilization, it is highly responsive to the stimulatory actions of gonadal steroids. Galanin gene expression and synthesis is activated under conditions of increased fat intake and fat deposition that precede periods of little feeding and increased fat oxidation. These include mid-to-late hours of the natural feeding cycle and the developmental period around puberty. The association between NPY and CORT may explain conditions of overeating and obesity associated with hypercortisolemia and insulin resistance. The association between gonadal steroids and GAL may be related to the enhanced intake and deposition of fat, after puberty, that may contribute to eating disorders