OBESITY ON A HIGH-FAT DIET - ROLE OF HYPOTHALAMIC GALANIN IN NEURONS OF THE ANTERIOR PARAVENTRICULAR NUCLEUS PROJECTING TO THE MEDIAN-EMINENCE

Previous studies have suggested that the peptide galanin (GAL) in the hypothalamus is related to the preference of an animal for dietary fat . The present report investigates this relationship further to identif y the specific GAL-synthesizing cell groups involved and to characteri ze their association to circulating glucose or hormones and their poss ible contribution to body fat deposition. Male albino Sprague Dawley r ats were tested in different feeding paradigms with diets containing t he macronutrients, fat, carbohydrate, or protein. These studies, using multiple techniques, identify a cell group in the hypothalamus that e xpresses GAL and that shows a shift in peptide activity in close relat ion to dietary fat, circulating glucose, and body fat. In all paradigm s, a rise in fat intake, from 10 to 30%, is associated with reduced le vels of insulin and corticosterone and normal glucose levels, whereas a further increase in fat ingestion (>30%) leads to hyperglycemia alon g with greater adiposity. In the hypothalamus, GAL gene expression, pe ptide production, and peptide release rise significantly (by 40%) in a ssociation with fat ingestion, showing no relation to either carbohydr ate or protein ingestion. This change is highly site specific, evident predominantly in GAL-synthesizing neurons in the anterior parvocellul ar region of the paraventricular nucleus (aPVN) and in GAL-containing terminals in the external zone of the median eminence (ME). Positive c orrelations detected between mRNA abundance in the aPVN and GAL peptid e in the ME support the existence of an aPVN-ME projection system rela ted to fat intake and fat deposition. When activated by dietary fat, t he contribution of this projection to body fat is suggested by consist ent positive correlations between aPVN-ME GAL and either dietary fat, circulating glucose, or body fat and by significantly higher GAL level s (+30%) in obesity-prone compared with obesity-resistant rats. This e vidence supports a role for this hypothalamic GAL projection system in the development of obesity produced by the overconsumption of fat.