Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: effect of different n-6/n-3 fatty acid ratios.
Male Fischer rats were fed the AIN 76A diet containing varying n-6/n-3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatectomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20:4n-6. In addition, there is an accumulation of 18:1 n-9 and 18:2n-6 and a decrease in the end products of the n-3 metabolic pathway in PC, suggesting a dysfunctional delta-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increase in the glutathione (GSH) concentration. The low n-6/n-3 FA ratio diets significantly decreased 20:4n-6 in PC and PE phospholipid fractions with a concomitant increase in 20:5n-3, 22:5n-3, and 22:6n-3. The resultant changes in the 20:4/20:5 FA ratio and the 20:3n-6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20:4n-6 in PE by equalizing the nodule/surrounding ratio. The low n-6/n-3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n-3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.
Abel
S
S
Medical Research Council, Tygerberg, South Africa. stefan.abel@mrc.ac.za
De Kock
M
M
Smuts
C M
CM
de Villiers
C
C
Swanevelder
S
S
Gelderblom
W C A
WC
D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D050602:Linoleoyl-CoA Desaturase; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008055:Lipids / Q000032:analysis; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D008055:Lipids; D011453:Prostaglandins; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D005982:Glutathione Transferase; D005978:Glutathione