title: Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  HPLC 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) (14)C-accumulation in CO2 and acid soluble products 2.9-fold from [1-(14)C]-oleic acid and 1.6-fold from [1-(14)C]-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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Laboratory of Developmental Nutrition, Department of Animal Sciences, North Carolina State University, Box 7621, Raleigh, NC 27695 USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Laboratory of Developmental Nutrition, Department of Animal Sciences, North Carolina State University, Box 7621, Raleigh, NC 27695 USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Jacobi
authors.affiliation: Laboratory of Developmental Nutrition, Department of Animal Sciences, North Carolina State University, Box 7621, Raleigh, NC 27695 USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Odle
keywords: Clofibrate; Fatty acid oxidation; Pigs; Placenta transfer