Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate.

Xi Lin,Jack Odle,Sheila Jacobi

doi:10.1186/s40104-015-0010-7

Abstract

BackgroundTo induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study. Each group of pigs (n = 10) was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were collected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.ResultsHPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow (~4.2 μg/mL) and its offspring (~1.5 μg/mL). Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased (P < 0.01) 14C-accumulation in CO2 and acid soluble products 2.9-fold from [1-14C]-oleic acid and 1.6-fold from [1-14C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO) activities by 36% and 42% over controls (P < 0.036). The mRNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate (P < 0.0001) but no differences were detected for ACO and PPARα mRNA between the two groups.ConclusionThese data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.

Highlights

To induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study
Plasma assay Chromatograms from HPLC analysis confirmed that clofibric acid was present in the plasma of both the clofibrate-fed sow and their newborn pigs (Figure 1)
In addition to clofibric acid, a clofibrate conjugate metabolite was detected in the plasma of the clofibrate-fed sow but not in the plasma of newborn pigs

Summary

Introduction

To induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study. Sow milk fat concentration is about 6% at birth and increases to 10% within 24 h. This is 67–70% higher than human colostrum (3.5–6%) and constitutes up to 60% of the energy in the milk, indicating that the milk fat is the primary energy source for newborn pigs after birth. It is critical for newborn pigs to use milk fat efficiently at birth to survive. Results from previous studies show that over 85% of the fatty acids taken up by newborn pig hepatocytes are re-esterified

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