Maternal Supplementation of Clofibrate Stimulates Hepatic Fatty Acid Oxidation in Newborn Suckling Piglets

Abstract

Objectives

To evaluate effects of maternal feeding of clofibrate, a PPARα agonist, on development of hepatic fatty acid metabolism in offspring using pig as a model.

Methods

Pregnant sows (N = 27) were randomly assigned into three treatment groups. Each group was fed a standard diet (3265 kcal ME/kg) supplemented with either 0, 0.25% or 5% clofibrate (w/w) from d 107 of gestation to d 7 of lactation. Liver tissue was collected from piglets at birth, d1, 7, 14 and 19. Fatty acid oxidation was examined in fresh homogenates using 1 mM [1–¹⁴C] oleic acid (9.9 mBq/mmol) as substrate. Oxidation was measured in the absence or presence of in vitro supplemented L-carnitine (1 mM) and/or malonate (5 mM).

Results

Clofibrate was not detected in piglet liver or sow milk. Interactions between clofibrate and postnatal age (P < 0.001) on the ¹⁴C accumulation in ¹⁴CO₂, acid soluble products (¹⁴C-ASP) and esterified products (¹⁴C-ESP) were observed. Accumulation in ¹⁴CO₂ was not altered by piglet age in control sows; however, accumulation in ¹⁴C-ASP was higher at d14 and lower at d19 compared to d1. In contrast, maternal clofibrate increased ¹⁴CO₂ by 100% and ¹⁴C-ASP by 80% in pigs at d1, and the increase was higher in pigs from sows given 0.5% versus 0.25% clofibrate. Accumulation in ¹⁴C-ESP in pigs from control sows increased from d1 to d14, but there was no difference detected between d14 and 19. Assessment of pigs from sows fed the 0.25% clofibrate dose revealed no impact on ¹⁴C-ESP, but the 0.5% dose increased ¹⁴C-ESP by 31%. No interaction was observed between clofibrate and the in vitro treatments (carnitine and malonate; P = 0.5). In vitro supplementation of carnitine increased radiolabel accumulation in CO₂ by 60% and in ASP by 120%, but reduced ¹⁴C-ESP by 39% compared to control incubations. Supplementation of malonate reduced ¹⁴CO₂ by 95% and ¹⁴C-ESP by 44%, but had no impact on ¹⁴C-ASP.

Conclusions

Maternal clofibrate enhances hepatic fatty acid metabolism in offspring, but the effect fades with postpartum age. The availability of carnitine in the milk could be a key element to support fatty acid oxidation in postnatal pigs.

Funding Sources

USDA National Institute of Food and Agriculture.