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.

Previous studies have shown that genes involved in fatty acid uptake, fatty acid oxidation, and thermogenesis are downregulated in liver and skeletal muscle of rats during lactation. However, biochemical mechanisms underlying these important metabolic adaptations during lactation have not yet been elucidated. As all these genes are transcriptionally regulated by peroxisome proliferator-activated receptor a (Ppara), we hypothesized that their downregulation is mediated by a suppression of Ppara during lactation. In order to investigate this hypothesis, we performed an experiment with lactating and nonlactating Ppara knockout and corresponding wild-type mice. In wild-type mice, lactation led to a considerable downregulation of Ppara, Ppar coactivators Pgc1a and Pgc1b, and Ppara target genes involved in fatty acid uptake, fatty acid oxidation, and thermogenesis in liver and skeletal muscle (P!0 . 05). Ppara knockout mice had generally a lower expression of all these Ppara target genes in liver and skeletal muscle. However, in those mice, lactation did not lower the expression of genes involved in fatty acid utilization and thermogenesis in liver and skeletal muscle. Expression levels of Ppara target genes in lactating wild-type mice were similar than in lactating or nonlactating Ppara knockout mice. In conclusion, the present findings suggest that downregulation of Ppara and its coactivators in tissues with high rates of fatty acid catabolism is responsible for the reduced utilization of fatty acids in liver and skeletal muscle and the reduced thermogenesis occurring in the lactating animal, which aim to conserve energy and metabolic substrates for milk production in the mammary gland.

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Recent studies indicated that reduction of milk triacylglycerol concentrations by dietary conjugated linoleic acid (CLA) involves an impairment of both de novo fatty acid synthesis and uptake of fatty acids from circulating triacylglycerol-rich lipoproteins into the mammary gland. However, nonesterified fatty acids (NEFA) in the plasma released from adipose tissue and taken up into the mammary gland by fatty acid transporters are a further important source of fatty acids available for milk triacylglycerol synthesis. Therefore, the aim of the present study was to investigate the effect of dietary CLA on plasma concentrations of NEFA and the expression of fatty acid transporters in the mammary glands of lactating rats fed either a CLA diet or a control diet. Dams fed diets with CLA had a greater concentration of NEFA in plasma than those fed the control diet. In addition, relative mRNA concentrations of fatty acid transporters (fatty acid translocase/CD36, fatty acid transport protein, and plasma membrane fatty acid binding protein) were about 45, 75, and 70% lower, respectively, in the mammary gland of dams fed diets with CLA compared with those fed the control diet. In conclusion, the present findings indicate that reduced uptake of circulating NEFA released from white adipose tissue into the mammary gland could also contribute to the reduction of milk triacylglycerol concentrations by dietary CLA in rats. The mechanism through which CLA inhibits expression of fatty acid transporters deserves further study.