Hypothalamic galanin and plasma leptin and ghrelin in the maintenance of energy intake in the Brattleboro rat.

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-carbohydrate 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.

Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, plasma leptin and body weight gain and composition.

The aim of this study was to determine the effects of the chronic ingestion of aspartame (ASP) on brain neuropeptide Y (NPY) concentrations, plasma hormones, food intake and body fat. Two groups of male Long-Evans rats, fed on a control (C) well-balanced diet, had to drink either a 0.1% ASP solution or water for a period of 14 weeks starting at weaning. Food intake and body weight were weekly recorded. At the end of the experiment, fat pads were sampled, leptin and insulin were measured in the plasma and NPY in several microdissected brain areas. Substituting ASP for water led to lower body weight (-8%; P<.004) and lower fat depot weight (-20%; P<.01) with no differences in energy intake or plasma insulin concentrations. Plasma leptin was significantly reduced by 34% (P<.05). Leptin concentrations were well-correlated with final body weight (r=.47; P<.025) and fat pad mass (r=.53; P<.01). NPY concentrations were 23% lower (P<.03) in the arcuate nucleus of ASP rats with no differences in other brain areas. The beneficial effects on body composition could be related to the decreased effects of NPY on lipid and energy metabolism, independently of insulin. The reasons for the NPY decrease (regulatory or toxicological) are not obvious. The constitutive amino acids of the ASP molecule might participate in the NPY regulation.