Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets

To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARa) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( +/- clofibrate) x 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-14C] palmitic acid (1 mM) as a substrate (0.265 mCi/mmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 mM) or acetoacetate-CoA deacylase (iodoacetamide, 50 mM). Without clofi-brate stimulation, 14C accumulation in CO2 was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased 14C-ASP (P < 0.0001) above all other treatments, regardless of clofibrate treatment. The percentage of 14C in CO2 was higher (P = 0.0023) in TC5 than in the control group. From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA (product of b-oxidation) via alteration of TCA cycle activity, but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARa. In addition, the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.(c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Supporting the anaplerotic and ketogenic fatty acids (FA) could potentially impact FA oxidation and modify the metabolism of acetyl-CoA via alteration of tricarboxylic acid (TCA) cycle activity. However, it has no significant effect on the hepatic FA oxidative capacity induced by peroxisome proliferator-activated receptor-alpha (PPARa). The availability of carnitine is crucial for maintaining FA oxidation during the neonatal period.