Peroxisome proliferators enhance linoleic acid metabolism in rat liver. Increased biosynthesis of omega 6 polyunsaturated fatty acids.
The alterations by peroxisome proliferators of metabolism of linoleic acid in rat liver were studied. Administration of P-chlorophenoxyisobutyric acid (clofibric acid) enhanced in vivo conversion of linoleic acid to its desaturated and/or elongated metabolites, 6,9,12-octadecatrienoic acid, 8,11,14-eicosatrienoic acid, and arachidonic acid, whereas the formation of 11,14-eicosadienoic acid was decreased. These changes observed in vivo were confirmed in vitro to be due to the increases in activities of delta 6 desaturation of linoleic acid to 6,9,12-octadecatrienoic acid (18.4 times), delta 8 desaturation of 11,14-eicosadienoic acid to 8,11,14-eicosatrienoic acid (3.4 times), and delta 5 desaturation of 8,11,14-eicosatrienoic acid to arachidonic acid (4.1 times). No considerable changes in activities of chain elongation of either linoleic acid or 6,9,12-octadecatrienoic acid were observed. The increases in the activities of three desaturations by clofibric acid were prevented by the treatment of rats with cycloheximide. The inductions of delta 6 and delta 5 desaturations were brought about by the treatment of rats with 2,2'-(decamethylenedithio)diethanol or di-(2-ethylhexyl)-phthalate, peroxisome proliferators structurally unrelated to clofibric acid, as well. These changes in metabolism of linoleic acid by clofibric acid were consistent with the changes in mass proportion of omega 6 fatty acids in hepatic lipid. Physiological significance of the marked changes in linoleic acid metabolism by peroxisome proliferators was discussed.
Kawashima
Y
Y
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Musoh
K
K
Kozuka
H
H
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000494:pharmacology*; D003066:Coenzyme A Ligases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000378:metabolism; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008042:Linolenic Acids / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D017965:gamma-Linolenic Acid; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008042:Linolenic Acids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D002995:Clofibric Acid; D017965:gamma-Linolenic Acid; D003513:Cycloheximide; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D015126:8,11,14-Eicosatrienoic Acid; D002994:Clofibrate