HYPOTHALAMIC GALANIN - CONTROL BY SIGNALS OF FAT-METABOLISM

The peptide, galanin (GAL), is known to stimulate eating behavior, red uce energy expenditure and affect the release of metabolic hormones. F urther, 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 meta bolism that may also affect GAL production and, through these neuroche mical events, control the ingestion of specific nutrients. Three exper iments were performed in normal-weight male, Sprague-Dawley rats. In E xperiment 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 Ex periment 3 studied mercaptoacetate (MA, 200 and 600 mu mol/kg), which blocks fatty acid oxidation. Eating behavior was examined in some rats , whereas hypothalamic GAL activity was measured in others using radio immunoassay, immunohistochemistry and in situ hybridization. Both food deprivation and MA (600 mu mol/kg), but not 2-DG, affected GAL in the hypothalamus, in one specific area. This is the anterior parvocellula r region of the paraventricular nucleus (aPVN), which has a dense conc entration of GAL-containing neurons and terminals. GAL gene expression and peptide immunoreactivity in this area is enhanced by food depriva tion; in contrast, it is reduced by injection of MA. Other hypothalami c 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 tha t these shifts in GAL activity are accompanied by specific changes in eating behavior. Food deprivation which enhances aPVN GAL produces a m arked increase in fat ingestion, whereas MA which reduces aPVN GAL cau ses 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. (C) 1998 Elsevier Science B.V. All righ ts reserved.