Feeding oxidized fat during pregnancy up-regulates expression of PPARα-responsive genes in the liver of rat fetuses

Abstract

BackgroundFeeding oxidized fats causes activation of peroxisome proliferator-activated receptor α (PPARα) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARα in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARα 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.ResultsIn both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARα-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 PPARα, 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).ConclusionThe present study demonstrates for the first time that components of oxidized fat with PPARα activating potential are able to induce a PPARα 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.

Activation of the nuclear receptor PPARα regulates lipid metabolism in foetal liver from diabetic rats: implications in diabetes‐induced foetal overgrowth

“…Moreover, diets supplemented with an overload of oxidized lipids, capable of activating PPARα, lead to an increase in the expression of PPARα and enzymes related to lipid oxidation in the foetal liver [56]. The experimental approach used in this work aimed to analyse foetal PPARα effects separately from the maternal effects.…”

Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

“…Supplementation with shorter chain fatty acids that could be readily oxidized did not rescue development, suggesting that longer chain fatty acid oxidation does occur and plays a vital role in mouse development. LCAD and many other mitochondrial b-oxidation enzymes (L-type carnitine palmitoyltransferase I and medium-chain acyl-CoA dehydrogenase) are regulated by PPARA (Ringseis et al 2007). This brings an interesting insight into our experiments.…”

Peroxisome proliferator-activated receptor α activation regulates lipid metabolism in the feto-placental unit from diabetic rats

“…Treatment of rats with pharmacological PPARa activators during pregnancy causes proliferation of peroxisomes and induction of peroxisomal enzyme activities in both maternal and fetal livers (Cibelli et al 1988, Peraza et al 2006. Reduction in maternal hypertriglyceridaemia has been found when rats are treated with fibrates during the whole pregnancy but not when treated only at term (Soria et al 2002, Ringseis et al 2007). These results suggest that PPARa is involved in the regulation of maternal lipid metabolism; however, direct effects of PPARa activation in lipid metabolism in the fetus and the placenta have not been reported yet and may be relevant in maternal diabetes.…”