Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs
AbstractThe 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 [1-14C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria (p < 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 (p < 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. View Full-Text
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He, Y.; Khan, I.; Bai, X.; Odle, J.; Xi, L. Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs. Int. J. Mol. Sci. 2017, 18, 2663.
He Y, Khan I, Bai X, Odle J, Xi L. Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs. International Journal of Molecular Sciences. 2017; 18(12):2663.Chicago/Turabian Style
He, Yonghui; Khan, Imad; Bai, Xiumei; Odle, Jack; Xi, Lin. 2017. "Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs." Int. J. Mol. Sci. 18, no. 12: 2663.
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