Alcoholic fatty liver results from an impaired fatty acid catabolism due to blockade of PPARalpha and increased lipogenesis due to activation of sterol regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF) and conjugated linoleic acids (CLA) have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent ethanol-induced triacylglycerol accumulation in the liver by upregulation of PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and fed isocaloric liquid diets containing either sunflower oil (SFO) as a control fat, OF prepared by heating of SFO, or CLA, in the presence and absence of ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA transferase I, and cytochrome P450 4A1 and increased triacylglycerol concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had similar mRNA concentrations of PPARalpha-responsive genes and similar triacylglycerol concentrations in the liver as rats fed SFO or CLA without ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid synthase were not altered by OF or CLA compared with SFO. This study shows that OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty acids, whereas CLA does not exert such an effect.

Feeding oxidized fats to lactating rats causes a strong reduction of triacylglycerol concentration in the milk. The reason for this, however, has not yet been elucidated. Pregnant Sprague-Dawley rats were assigned to 2 groups of 11 rats each and fed diets containing either fresh fat (FF group) or an oxidized fat (OF group) from d 1 to d 20 of lactation. Concentrations of triacylglycerols and long-chain fatty acids in the milk and weight gain of suckling pups were lower in the OF group than in the FF group (P < 0.05). Concentrations of medium-chain fatty acids in the milk and messenger RNA (mRNA) abundance of lipogenic enzymes in the mammary gland did not differ between the 2 groups of rats. However, the OF group had a lower concentration of triacylglycerols and nonesterified fatty acids (NEFA) in plasma and lower mRNA concentrations of lipoprotein lipase and fatty acid transporters in the mammary gland than the FF group (P < 0.05). Moreover, the OF group had higher mRNA concentrations of hepatic lipase, fatty acid transporters, and several genes involved in fatty acid oxidation in the liver than the FF group (P < 0.05). The present findings suggest that a dietary oxidized fat lowers the concentration of triacylglycerols in the milk by a reduced uptake of fatty acids from triacylglycerol rich-lipoproteins and NEFA into the mammary gland. The study, moreover, indicates that an oxidized fat impairs normal metabolic adaptations during lactation, which promote the utilization of metabolic substrates by the mammary gland for the synthesis of milk.