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

Abstract

Maintaining an active fatty acid metabolism is important for renal growth, development, and health. We evaluated the effects of anaplerotic and ketogenic energy sources on fatty acid oxidation during stimulation with clofibrate, a pharmacologic peroxisome proliferator-activated receptor α (PPARα) agonist. Suckling newborn pigs (n = 72) were assigned into 8 dietary treatments following a 2 × 4 factorial design: ± clofibrate (0.35%) and diets containing 5% of either (1) glycerol-succinate (GlySuc), (2) tri-valerate (TriC5), (3) tri-hexanoate (TriC6), or (4) tri-2-methylpentanoate (Tri2MPA). Pigs were housed individually and fed the iso-caloric milk replacer diets for 5 d. Renal fatty acid oxidation was measured in vitro in fresh tissue homogenates using [1-14C]-labeled palmitic acid. The oxidation was 30% greater in pig received clofibrate and 25% greater (p < 0.05) in pigs fed the TriC6 diet compared to those fed diets with GlySuc, TriC5, and Tri2MPA. Addition of carnitine also stimulated the oxidation by twofold (p < 0.05). The effects of TriC6 and carnitine on palmitic acid oxidation were not altered by clofibrate stimulation. However, renal fatty acid composition was altered by clofibrate and Tri2MPA. In conclusion, modification of anaplerosis or ketogenesis via dietary substrates had no influence on in vitro renal palmitic acid oxidation induced by PPARα activation.

Intestinal Carnitine Status and Fatty Acid Oxidation in Response to Clofibrate and Medium-Chain Triglyceride Supplementation in Newborn Pigs

“…Activation of peroxisome proliferator-activated receptor alpha (PPARα) increase expression of genes associated with carnitine synthesis such as γ-butyrobetaine hydroxylase (BBOX), N-6-trimethyllysine dioxygenase (TMLHE), and 4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1) and transport such as OCTN2 as well as carnitine concentrations in many tissues in adult animals [ 14 , 15 , 16 ]. In addition, activation of PPARα also stimulates fatty acid oxidation in liver, kidney and muscle via inducing gene expressions and increasing activities of carnitine palmitoyltransferase I (CPT I), acyl-CoA oxidase (ACOX) and malonyl-CoA decarboxylase (MCD) [ 17 , 18 , 19 , 20 , 21 , 22 ]. As a pharmaceutical PPARα agonist, clofibrate can activate PPARα, modulating CPT I gene expression and increasing fatty acid oxidation in pigs and other species [ 23 , 24 , 25 , 26 ].…”