Clofibrate increases in vivo fatty acid oxidation by neonatal pigs

Abstract

To test the effect of clofibrate on the fatty acid (FA) oxidation in vivo, newborn pigs received 5 mL of vehicle (2% tween 80) with or without clofibrate (75 mg/kg bw) once daily via intragastric gavage for 3 days. Total FA oxidative capacity was measured in respiration chambers after gastric infusion of piglets (n=5/treatment) with isoenergetic amounts of [1‐14C] labeled triglycerides (TG) ‐‐ either tri‐C18:1 (3.02 mmol/kg bw0.75) or tri‐ C22:1 (2.46 mmol/kg bw0.75). Total expired 14CO2 was collected and quantified at 20‐min intervals over 24 h. Hepatic in vitro FA oxidation was determined simultaneously using [1‐14C] labeled C18:1 and C22:1. The average 24 h accumulative [1‐14C] TG oxidative utilization (% of energy intake/kg bw0.75) tended to increase with clofibrate supplementation (P<0.14), but there was no difference in the peak utilization rate. The maximal extent of tri‐C18:1 oxidation was 61 % greater than for tri‐C22:1. Hepatic FA oxidation in vitro increased significantly with clofibrate. The relative abundance of mRNA increased 2–3 fold for hepatic PPARα and its target genes (fatty acyl‐CoA oxidase (FAO), carnitine palmitoyltranserase (CPT) I and CPT II) in the pigs given clofibrate. The increase in mRNA enrichment by clofibrate was greater for CPT I than for ACO. In conclusion, clofibrate may improve in vivo FA oxidative utilization in neonatal pigs. Supported by CSREES, USDA NRI program award 2007‐35206‐17897.