DIFFERENTIAL-EFFECTS OF INTRACEREBROVENTRICULAR GLUCAGON-LIKE PEPTIDE-1 ON FEEDING AND ENERGY-EXPENDITURE REGULATION

Intracerebroventricular (ICV) administration of glucagon-like peptide- 1-(7-37) amide (GLP-1) has been shown to modulate food and water intak e. The present studies further characterize the effects of ICV GLP-1 i n the regulation of energy balance in lean and obese animals. In both obese and lean Zucker rats, a single ICV infusion of GLP-1 (1-30 mu g) resulted in a dose-dependent reduction of food intake and decrease in respiratory quotient relative to the saline control during the first 2 h of the nocturnal cycle. In obese Zucker rats, the food intake was reduced by 73 +/- 11% of the control at the 30 mu g dose, whereas a mo dest 45 +/- 18% reduction was observed in lean rats. Despite the large reduction in food intake seen with GLP-1, there was no compensatory d ecrease in nocturnal oxygen consumption in the obese Zucker rats. Inte restingly, low doses of GLP-1 (1 mu g) in lean Zucker rats, which had minimal effects on food intake, caused a 19 +/- 7% increase in O-2 con sumption during the first 2 h of the nocturnal cycle. These data sugge st that central GLP-1 may be an important factor controlling negative energy balance in both the lean and obese Zucker rats. (C) 1998 Elsevi er Science Inc.