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 identify the specific GAL-synthesizing cell groups involved and to characterize their association to circulating glucose or hormones and their possible contribution to body fat deposition. Male albino Sprague Dawley rats were tested in different feeding paradigms with diets containing the macronutrients, fat, carbohydrate, or protein. These studies, using multiple techniques, identify a cell group in the hypothalamus that expresses GAL and that shows a shift in peptide activity in close relation to dietary fat, circulating glucose, and body fat. In all paradigms, a rise in fat intake, from 10 to 30%, is associated with reduced levels of insulin and corticosterone and normal glucose levels, whereas a further increase in fat ingestion (>30%) leads to hyperglycemia along with greater adiposity. In the hypothalamus, GAL gene expression, peptide production, and peptide release rise significantly (by 40%) in association with fat ingestion, showing no relation to either carbohydrate or protein ingestion. This change is highly site specific, evident predominantly in GAL-synthesizing neurons in the anterior parvocellular region of the paraventricular nucleus (aPVN) and in GAL-containing terminals in the external zone of the median eminence (ME). Positive correlations detected between mRNA abundance in the aPVN and GAL peptide in the ME support the existence of an aPVN-ME projection system related to fat intake and fat deposition. When activated by dietary fat, the contribution of this projection to body fat is suggested by consistent positive correlations between aPVN-ME GAL and either dietary fat, circulating glucose, or body fat and by significantly higher GAL levels (+30%) in obesity-prone compared with obesity-resistant rats. This evidence supports a role for this hypothalamic GAL projection system in the development of obesity produced by the overconsumption of fat.