Background: We have previously shown that a high-fat diet enriched with polyunsaturated fatty acids (PUFA-ω-3) has a protective effect on hepatic ischemia-reperfusion injury, but the mechanisms have not been clarified. Peroxisome proliferator-activated receptor alpha (PPAR-α) is a member of the nuclear receptor superfamily highly expressed in liver and up-regulates the expression of a number of genes involved in hepatic fatty acid metabolism. Studies have demonstrated that PUFA-ω-3 increases the fatty acid oxidation through activation of PPRA-α.
Aim: Given the known that PUFAs-ω-3 regulates the expression of genes in various tissues, including the liver, the objective of this study was to evaluate the role of a high-fat diet enriched with PUFAs-ω-3 (fish oil) in the hepatic expression of PPAR-α in Wistar rats.
Methods: Wistar male rats were divided in 2 groups: Group I (n=10): rats with fatty liver induced by high-fat enriched with PUFAs-ω-3 for 4 weeks and Group II (n=10): received standard diet. After this period, the animals were sacrificed and their livers were collected for histologic examination, determination of oxidation and phosphorylation of liver mitochondrial, and mRNA isolation. The analyses of PPAR-α gene expression were performed by Quantitative PCR (qPCR) using specific primers for PPAR-α and the results were normalized according to corresponding values of housekeeping β-actin mRNA. Serum aminotransferases (AST, ALT) were also analyzed.
Results: Mild liver steatosis was observed in the periportal area in the Group I in comparison to group that received standard diet. The PUFA-ω-3 group had a significant liver mitochondrial function deviation: RCR (3.09 ± 0,22 vs 3.73 ± 0.14) and respiration state 4 (23.59 ± 1.97 vs 15.47 ± 1.35 nmol O2mgprot/min) in relation to group II, with a standard diet (p<0.05). AST and ALT levels were similar in the animals receiving both diets. There was no significant modification in PPAR-α mRNA content in the group I when compared with the group that received standard diet.
Conclusion: Although the interaction of nuclear receptors and transcription factors with PUFAs has been shown to be critical to the regulation of several key genes of lipid metabolism, these findings suggest that the protective effect of a high-fat diet enriched with PUFA ω-3 is not through PPAR-α pathways. Probably genes related to inflammatory process and to hepatic fatty acid synthesis can be involved. Further studies are necessary to provide insights about this protective effect on steatosis and in hepatic ischemia-reperfusion injury.