MODIFICATION OF MEMBRANE LIPID COMPOSITION AND MIXED-FUNCTION OXIDASES IN MOUSE LIVER MICROSOMES BY DIETARY TRANS FATTY ACIDS (CYTOCHROME P-450, P-448).

摘要

C57Bl/6J male mice were fed control diets or experimental diets (containing 25% trans fatty acids from margarine). Both low fat (10% w/w) and high fat (20% w/w) diets were used. Liver microsomes isolated from these animals at selected ages were examined for: cytochromes P-450 content; substrate binding profiles; specific activity of cytochromes P-450/448 as measured by ethoxyresorufin O-deethylation and other cytochromes P-450 as measured by ethoxycoumarin O-dealkylation; electrophoretic patterns of microsomal proteins; fluidity of selected membranes; phospholipid profiles of microsomal fractions; and fatty acid composition of total, polar, neutral and individual lipid classes of membrane lipids. Relative to the controls, the liver total microsomes, rough microsomes, or smooth microsomes that were isolated from animals on the experimental diet showed: decreased substrate binding of 1-butanol, chloroform, cyclohexane or ethoxyresorufin; increased total cytochromes P-450 content as measured by carbon monoxide difference spectra; increased specific activity of cytochromes P-448/450 as measured by ethoxyresorufin O-deethylation; decreased specific activity of cytochromes P-450 as measured by ethoxycoumarin O-dealkylation; increased fluidity of rough microsomal membrane as measured by fluorescence polarization; increased amounts of cytochromes with molecular weight 53,000 and 55,000 on SDS-polyacrylamide gel electrophoresis; altered lipid class profiles as determined by thin layer chromatography; and altered fatty acid composition of membrane lipids as determined by capillary gas-liquid chromatography with an increased ratio of linoleic acid to arachidonic acid (18:2/20:4) and decreased palmitic acid (16:0), stearic acid (18:0), and oleic acid (cis-18:1) in most fractions. Percentages of trans fatty acids seen in the different lipid fractions of microsomal membranes ranged from 3.5 to 15.2% for the low fat experimental diet and 6.9 to 12.9% for the high fat experimental diet. An important finding in this study was that animals fed experimental diets containing trans fatty acids have increased activity of the cytochromes P-450/448 mixed function oxidases. This is indirect evidence of increased benz a pyrene type xenobiotic metabolism known to be important in chemical carcinogenesis. Possible mechanisms whereby the trans fatty acids are responsible for the observed effect are discussed.