Downregulation of peroxisome proliferator-activated receptor alpha and its coactivators in liver and skeletal muscle mediates the metabolic adaptations during lactation in mice.

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 alpha (Pparalpha), we hypothesized that their downregulation is mediated by a suppression of Pparalpha during lactation.

Mouse carnitine-acylcarnitine translocase (CACT) is transcriptionally regulated by PPARalpha and PPARdelta in liver cells.

Background: Hepatic PPARalpha acts as the primary mediator of the adaptive response to fasting by upregulation of a number of genes involved in fatty acid catabolism. Whether carnitine-acylcarnitine translocase (CACT), which mediates the import of acylcarnitines into the mitochondrial matrix for subsequent beta-oxidation of fatty acid moieties, is also regulated by PPARalpha in the liver has not yet been investigated.

Methods And Results: Herein, we observed that hepatic mRNA abundance of CACT was increased by both, fasting and treatment with PPARalpha agonist WY-14,643 in wild-type mice but not PPARalpha-knockout mice (P<0.

Peroxisome proliferator-activated receptor alpha and enzymes of carnitine biosynthesis in the liver are down-regulated during lactation in rats.

This study investigated the hypothesis that lactation lowers gene expression of peroxisome proliferator-activated receptor (PPAR) alpha in the liver and that this leads to a down-regulation of hepatic enzymes involved in carnitine synthesis and novel organic cation transporters (OCTNs). Thirty-two pregnant female rats were divided into 4 groups. In the first group, all pups were removed, whereas in the other groups, litters were adjusted to sizes of 4, 10, or 18 pups per dam.

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.