Galanin, ghrelin, and leptin are three peptides involved in feeding regulation and more particularly in fat intake. The Brattleboro (di/di) rat is a genetic model of diabetes insipidus characterized by a preference for fat when it is in a food choice situation. Here, we measured hypothalamic galanin concentrations. plasma ghrelin and leptin and dietary preferences of adult di/di Brattleboro rats, di/+ and Long-Evans controls. The Brattleboro rats weighed significantly less than the di/+ rats (-18%; P < 0.001). The fat-to-carbo hydrate intake ratio was significantly greater in Brattleboro rats than in di/+ (P < 0.02) when the rats could choose between a high-fat diet and a high-carbohydrate diet. Galanin concentrations were significantly lower in di/di rats than in di/+ rats in the paraventricular nucleus (-56%; P < 0.001) but not in the arcuate nucleus. Plasma leptin was significantly lower in the di/di rats than in the di/+ rats (3.49 +/-0.20 vs. 6.94 +/- 0.49 ng/ml; P < 0.001). Plasma ghrelin concentrations were significantly lower in Long-Evans rats than in the di/di rats (-21%; P < 0.01). Given that galanin mRNA is overexpressed in the paraventricular nucleus of Brattleboro rats, these data are consistent with increased release of the peptide. In the Brattleboro rat, this overactive galanin system and the variations of ghrelin and leptin maintain an orexigenic drive favoring a preferential intake of fat which provides the animal with enough energy for its metabolism. (C) 2007 Elsevier Inc. All rights reserved.