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J. Biol. Chem., Vol. 265, Issue 16, 9170-9175, Jun, 1990
Y Kawashima, K Musoh and H Kozuka
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.
Peroxisome proliferators enhance linoleic acid metabolism in rat liver. Increased biosynthesis of omega 6 polyunsaturated fatty acids
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
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