Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs

• Published in: International journal of molecular sciences 2017-12, Vol.18 (12), p.2663
• Main Authors: He, Yonghui, Khan, Imad, Bai, Xiumei, Odle, Jack, Xi, Lin
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - biosynthesis; Activation; Animals; Antimycin A; Body weight; Carnitine; Carnitine palmitoyltransferase; clofibrate; Clofibrate - administration & dosage; Coenzyme A; Enzyme activity; fatty acid β-oxidation; Fatty acids; Fatty Acids - biosynthesis; Fatty Acids - genetics; Fuel consumption; Hydroxymethylglutaryl-CoA Synthase - biosynthesis; Ketogenesis; Kidney - drug effects; Kidney - metabolism; Kidneys; Lipid Metabolism - genetics; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; mRNA; Oleic acid; Oxidation; Oxidation rate; Oxidation-Reduction; Palmitoyltransferase; peroxisome proliferator-activated receptor α (PPARα); Peroxisome proliferator-activated receptors; Peroxisomes; Peroxisomes - genetics; Peroxisomes - metabolism; pigs; PPAR alpha - genetics; Rotenone; Suidae; Swine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18122663

The objective of this study was to evaluate the effects of peroxisome proliferator-activated receptor α (PPARα) activation by clofibrate on both mitochondrial and peroxisomal fatty acid oxidation in the developing kidney. Ten newborn pigs from 5 litters were randomly assigned to two groups and fed either 5 mL of a control vehicle (2% Tween 80) or a vehicle containing clofibrate (75 mg/kg body weight, treatment). The pigs received oral gavage daily for three days. In vitro fatty acid oxidation was then measured in kidneys with and without mitochondria inhibitors (antimycin A and rotenone) using [1- C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria ( < 0.001) but not in peroxisomes. In addition, the oxidation rate of C18:1 was greater in mitochondria than peroxisomes, while the oxidation of C22:1 was higher in peroxisomes than mitochondria ( < 0.001). Consistent with the increase in fatty acid oxidation, the mRNA abundance and enzyme activity of carnitine palmitoyltransferase I (CPT I) in mitochondria were increased. Although mRNA of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHMGCS) was increased, the β-hydroxybutyrate concentration measured in kidneys did not increase in pigs treated with clofibrate. These findings indicate that PPARα activation stimulates renal fatty acid oxidation but not ketogenesis.