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

• Published in: International journal of molecular sciences 2023-03, Vol.24 (7), p.6066
• Main Authors: Pike, Brandon, Zhao, Jinan, Hicks, Julie A, Wang, Feng, Hagen, Rachel, Liu, Hsiao-Ching, Odle, Jack, Lin, Xi
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anticholesteremic agents; Biosynthesis; Carbon sources; Carnitine; Carnitine - metabolism; Carnitine - pharmacology; Clofibrate - pharmacology; Diet; Dietary Supplements; Energy; Factorial design; fatty acid oxidation; Fatty acids; Fatty Acids - metabolism; Gene expression; Genetic aspects; Glycerol; Hogs; Intestine; Intestines; Liver; Liver - metabolism; medium-chain fatty acid; Milk; Neonates; Newborn babies; newborn pigs; Oxidation; Oxidation rate; Oxidation-Reduction; Oxidation-reduction reaction; Palmitic acid; Palmitic Acid - pharmacology; Peroxisome proliferator-activated receptors; Physiological aspects; Plasma; Proteins; Saturated fatty acids; Small intestine; Swine; Triglycerides; Triglycerides - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076066

To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in carnitine status and intestinal fatty acid oxidation in neonates, a total of 72 suckled newborn piglets were assigned into 8 dietary treatments following a 2 (±0.35% clofibrate) × 4 (diets with: succinate+glycerol (Succ), tri-valerate (TC5), tri-hexanoate (TC6), or tri-2-methylpentanoate (TMPA)) factorial design. All pigs received experimental milk diets with isocaloric energy for 5 days. Carnitine statuses were evaluated, and fatty acid oxidation was measured in vitro using [1- C]-palmitic acid (1 mM) as a substrate in absence or presence of L659699 (1.6 µM), iodoacetamide (50 µM), and carnitine (1 mM). Clofibrate increased concentrations of free (41%) and/or acyl-carnitine (44% and 15%) in liver and plasma but had no effects in the intestine. The effects on carnitine status were associated with the expression of genes involved in carnitine biosynthesis, absorption, and transportation. TC5 and TMPA stimulated the increased fatty acid oxidation rate induced by clofibrate, while TC6 had no effect on the increased fatty acid oxidation induced by clofibrate ( > 0.05). These results suggest that dietary clofibrate improved carnitine status and increased fatty acid oxidation. Propionyl-CoA, generated from TC5 and TMPA, could stimulate the increased fatty acid oxidation rate induced by clofibrate as anaplerotic carbon sources.