Clofibrate Increases Long-Chain Fatty Acid Oxidation by Neonatal Pigs

Abstract

Clofibrate may improve in vivo LCFA oxidative utilization in neonatal pigs.

Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate

“…In contrast with C24:0, high 14 C accumulations in CO 2 , ASP and CO 2  + ASP from C18:1 were observed in both mitochondria and peroxisomes, suggesting that C18:1can be oxidized initially in both of the organelles. Similar results were observed also using C18:1 and erucic acid as substrates in our previously study [13]. …”

“…The increase appears to be associated with the enhanced CPT I and ACO specific activities in the liver. The results achieved in the newborns exposed to clofibrate prenatally via the maternal diet were similar to the increase in vitro and vivo fatty acid oxidation reported in neonatal pigs receiving clofibrate directly postnatally [10,13]. Because the increase of CPT I specific activity was congruent with the great increase in mRNA expression, the stimulation of fatty acid oxidation in the liver, particularly in the mitochondria, resulted from the gene expression potentially due to the activation of PPARα by clofibrate.…”

“…The measurements followed the same procedure as described previously by Lin et al [5]. Specifically, liver homogenates (~40 mg) were incubated in 25 mL Erlenmeyer flasks with a final of volume of 2 mL of the reaction medium with or without addition of antimycin A (50 μmol/L) and rotenone (10 μmol/L) described as previously [13] for determining peroxisomal β-oxidation by inhibition of the electron transport chain of oxidative phosphorylation. The reaction was initiated by adding 2 μmol of either [1- 14 C]-C18:1 (4.2 MBq/mmol) or [1- 14 C]-C24:0 (1 MBq/mmol) and terminated by adding 0.5 mL HCLO 4 .…”

“…Recently we have demonstrated that supplementation of clofibrate could improve in vivo fatty acid oxidation in neonatal pigs [13]. However, increasing the fatty acid oxidative capacity of pigs at birth appears to be the key to improving energy utilization and increasing survivability.…”

Effects of Dietary Anaplerotic and Ketogenic Energy Sources on Renal Fatty Acid Oxidation Induced by Clofibrate in Suckling Neonatal Pigs

“…The induction of renal fatty acid oxidation via activation of PPARα occurred with the same pattern as observed in the liver of neonatal pigs [19]. Although renal β-oxidation was increased as previously observed [13], the increase had a minimal impact on ketogenesis probably due to a limited activity of HMGCS, owing to a posttranscriptional defect described in pigs [20].…”