Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure

OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a beta3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 mug/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54% increase in daily food intake and a 12% increase in body weight. An 8% decrease in VO2 measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.