Feeding oxidized fat during pregnancy up-regulates expression of PPARalpha-responsive genes in the liver of rat fetuses.
BACKGROUND
Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARalpha in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARalpha response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed.


RESULTS
In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARalpha-responsive genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARalpha, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05).


CONCLUSIONS
The present study demonstrates for the first time that components of oxidized fat with PPARalpha activating potential are able to induce a PPARalpha response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers.
Ringseis
Robert
R
Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany. robert.ringseis@landw.uni-halle.de
Gutgesell
Anke
A
Dathe
Corinna
C
Brandsch
Corinna
C
Eder
Klaus
K
D042964:Acyl-CoA Dehydrogenase / Q000235:genetics; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics; D042962:Acyl-CoA Oxidase / Q000235:genetics; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002994:Clofibrate / Q000494:pharmacology; D042926:Cytochrome P-450 CYP4A / Q000235:genetics; D004041:Dietary Fats / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism*; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics
D000924:Anticholesteremic Agents; D004041:Dietary Fats; D047493:PPAR alpha; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D019014:fas Receptor; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002334:Carnitine O-Palmitoyltransferase; D048031:JNK Mitogen-Activated Protein Kinases; D002994:Clofibrate