Hypothalamic galanin: control by signals of fat metabolism

The peptide, galanin (GAL), is known to stimulate eating behavior, reduce energy expenditure and affect the release of metabolic hormones. Further, the activity of this peptide in the hypothalamus is modulated, in turn, by these hormones as well as by the ingestion of nutrients. The focus of this investigation is on signals related to nutrient metabolism that may also affect GAL production and, through these neurochemical events, control the ingestion of specific nutrients. Three experiments were performed in normal-weight male, Sprague-Dawley rats. In Experiment 1, the impact of food deprivation (24 and 48 h) was examined. Experiment 2 tested the effects of the compound, 2-deoxy-D-glucose (2-DG, 200 and 400 mg/kg), which blocks glucose utilization, whereas Experiment 3 studied mercaptoacetate (MA, 200 and 600 micromol/kg), which blocks fatty acid oxidation. Eating behavior was examined in some rats, whereas hypothalamic GAL activity was measured in others using radioimmunoassay, immunohistochemistry and in situ hybridization. Both food deprivation and MA (600 micromol/kg), but not 2-DG, affected GAL in the hypothalamus, in one specific area. This is the anterior parvocellular region of the paraventricular nucleus (aPVN), which has a dense concentration of GAL-containing neurons and terminals. GAL gene expression and peptide immunoreactivity in this area is enhanced by food deprivation; in contrast, it is reduced by injection of MA. Other hypothalamic sites with dense concentrations of GAL-containing neurons or fibers are unaffected by food deprivation or MA, and the antimetabolite 2-DG has no impact on GAL in any area. Behavioral measurements indicate that these shifts in GAL activity are accompanied by specific changes in eating behavior. Food deprivation which enhances aPVN GAL produces a marked increase in fat ingestion, whereas MA which reduces aPVN GAL causes a specific reduction in fat ingestion along with a stimulation of protein intake. In contrast, 2-DG preferentially enhances ingestion of carbohydrate. These findings suggest a possible relationship between GAL activity in the aPVN and the metabolic and behavioral processes of fat metabolism and ingestion.