Abstract
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.
Highlights
The alterations by peroxisome proliferators of metabolism of linoleic acid in rat liver were studied
These changes observed in vivo were confirmed in vitro to be due to the increases in activities of A6 desaturation of linoleic acid to 6,9,12-octadecatrienoic acid (18.4 times), A8 desaturation of 11,14-eicosadienoic acid to 8,11,14
The marked increase in the formation of 18:l by peroxisome proliferators let us infer that these chemicals cause great changes in the metabolism of polyunsaturated fatty acids in liver, since appropriate proportion of polyunsaturated fatty acids in cellular phospholipid is necessary for maintaining physiological function of the cells
Summary
The alterations by peroxisome proliferators of metabolism of linoleic acid in rat liver were studied. 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 w6 fatty acids in hepatic lipid. Physiological significance of the marked changes in linoleic acid metabolism by peroxisome proliferators was discussed. The marked increase in the formation of 18:l by peroxisome proliferators let us infer that these chemicals cause great changes in the metabolism of polyunsaturated fatty acids in liver, since appropriate proportion of polyunsaturated fatty acids in cellular phospholipid is necessary for maintaining physiological function of the cells. Upon the administration of clofibric acid to rats, the increased formation of 20:4 took place by inducing desaturases of polyunsaturated fatty acids.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
