Unraveling the Pathway of Lipid Oxidation in the Young Pig: Assessment of Hepatic beta-oxidation and Characterization of Carnitine Palmitoyltransferase I (CPT I)

Abstract

Hepatic β-oxidation and liver and skeletal muscle carnitine palmitoyltransferase I (CPT I) activity and mRNA expression were evaluated in the pig. In the first study, newborn pigs were allotted to one of four dietary regimens: artificial milk replacer with long chain triglycerides (LCT) as the fat source (Control), the Control diet with 0.5% clofibric acid (CA), the Control diet with medium chain triglycerides replacing LCT as the fat source (MCT), or the Control diet with 40 ppm isoproterenol (ISO). There were no differences between Control and MCT or ISO supplemented groups in total, mitochondrial, or peroxisomal β-oxidation of [1-¹⁴C]-palmitate (1 mM). Total and peroxisomal β-oxidation increased 134 and 186%, respectively, with CA supplementation. Hepatic malonyl-CoA sensitive CPT activity increased (p < 0.05) in pigs receiving CA. Changes in relative expression of hepatic LCPT I and skeletal muscle MCPT I mRNA amounts following clofibrate supplementation were not detected, while a modest effect on acyl-CoA oxidase (ACO) relative mRNA amounts was observed (p=0.08). In the second study, hepatic and skeletal muscle CPT I kinetics in pigs during different stages of development were evaluated. Activity of CPT I increased 109 and 67% between birth and 1 wk of age in liver and skeletal muscle, respectively (p < 0.05). Realtive expression of hepatic CPT I mRNA in the 24 hr old pig was 7% of the amount detected in the newborn (p < 0.001); while hepatic CPT I apparent Km for carnitine decreased 48% from birth to 3 wk of age. The apparent Km for carnitine in skeletal muscle decreased from birth to 1 wk of age, then increased 200% between 1 and 5 wk of age (p< 0.01). Plasma and liver free carnitine concentrations increased 200 and 160%, respectively, during the first day of life (p < 0.05). High relative expression of γ-butyrobetaine hydroxylase (γBBH) in the kidney indicated high capacity for de novo carnitine synthesis by this tissue. Collectively, the findings from this research are important in understanding how the pig, a species with a low capacity for β-oxidation, utilizes fatty acids.