EFFECT OF EMERIAMINE, AN INHIBITOR OF FATTY-ACID OXIDATION, ON METABOLIC-FATE OF A GEOMETRICAL ISOMER OF LINOLEIC-ACID IN PERFUSED-RAT-LIVER

To estimate the relative significance of exogenous vs. endogenous fatt y acids in increasing hepatic triacylglycerol secretion following an i nhibition of fatty acid oxidation by emeriamine, livers from 2-d-fasti ng rats were perfused with or without an inhibitor in the presence of a geometrical isomer of linoleate (linolelaidic acid, trans,trans-9,12 -octadecadienoic acid). Emeriamine added to the perfusion medium at 2 h of the recirculating perfusion period caused immediate and complete cessation of ketone body production while it increased triacylglycerol and cholesterol secretion by the liver without affecting uptake of ex ogenous linolelaidic acid. The increase in the triacylglycerol secreti on by emeriamine was accompanied by a marked increase in the proportio n of linolelaidic acid in this lipid molecule in the perfusate and in the liver. The calculated amounts of exogenous linolelaidate, compared with those of endogenous fatty acids in the secretory triacylglycerol , suggested that the former compared with the latter contributes more to the drug-mediated increase in triacylglycerol secretion. This drug caused a marked reduction of mitochondrial carnitine palmitoyltransfer ase activity in perfused liver. These results suggest that a blockade of fatty acid oxidation by emeriamine, through an inhibition of carnit ine palmitoyltransferase, diverts predominantly the exogenous free fat ty acids from oxidation to the esterification pathway and subsequently stimulates the synthesis and secretion of triacylglycerol-rich lipopr oteins.