DEVELOPMENT OF INDEPENDENT INGESTIVE RESPONDING TO BLOCKADE OF FATTY-ACID OXIDATION IN RATS

The present studies examined the development of ingestive responsivene ss to blockade of fatty acid oxidation in rat pups using 2-mercaptoace tate (IIIA), an inhibitor of mitochondrial acyl-coenzyme A dehydrogena ses, or methyl palmoxirate (MP), an inhibitor of carnitine palmitoyltr ansferase I (CPT-I). Rat pups aged 6, 9, 12, or 15 days of age receive d an intraperitoneal injection of 0, 100, 200, 400, or 800 mu mol/kg M A, and intake of a commercial half-and-half or 15% glucose diet from t he floor of test containers was assessed in a 30-min test beginning 1 h after administration of MA. The results demonstrate that, although n o dose of MA affected intake of either diet in pups 9 days or younger, low doses of MA increased intake and the highest dose suppressed inta ke of both diets in pups 12 days of age or older. Physiological measur ements indicated that levels of beta-hydroxybutyrate were significantl y lower following doses of 400 or 800 mu mol/kg MA in 9-, 12-, and 15- day-old pups and that gastric emptying was inhibited in 12 and 15 day olds by 800 mu mol/kg MA. Intake of a commercial half-and-half diet fr om the floor of test containers was also assessed in 12- to 18-day-old rat pups 6.5 h after they received a gavage load of 0, 1.25, 2.5, 5, or 10 mg/kg MP. Unlike MA, MP did not increase intake of a commercial half-and-half diet in rat pups 12 or 15-18 days of age; instead, the h ighest dose of MP suppressed intake in 15- to 18-day-old pups. The fai lure of MP to enhance intake in pups at the ages tested is likely rela ted to composition of dam's milk; rat milk is high in medium-chain fat ty acids that do not require CPT-I for entry into mitochondria. Thus i t is likely that MP does not significantly block fatty acid oxidation in pups at the ages tested. On the other hand, blockade of fatty acid oxidation produced by MA significantly affects intake by 12 days of ag e, suggesting it may he the first metabolic signal that influences int ake in rat pups.