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 fatty acids in increasing hepatic triacylglycerol secretion following an inhibition of fatty acid oxidation by emeriamine, livers from 2-d-fasting 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 exogenous linolelaidic acid. The increase in the triacylglycerol secretion by emeriamine was accompanied by a marked increase in the proportion 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 palmitoyltransferase activity in perfused liver. These results suggest that a blockade of fatty acid oxidation by emeriamine, through an inhibition of carnitine palmitoyltransferase, diverts predominantly the exogenous free fatty acids from oxidation to the esterification pathway and subsequently stimulates the synthesis and secretion of triacylglycerol-rich lipoproteins.
Fukuda
N
N
Department of Biological Resource Sciences, Faculty of Agriculture, Miyazaki University, Japan.
Fukui
M
M
Kai
Y
Y
Jayasooriya
A P
AP
Sakono
M
M
Maeda
H
H
Ide
T
T
Yamamoto
K
K
D020155:3-Hydroxybutyric Acid / Q000032:analysis; D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002331:Carnitine; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007657:Ketone Bodies / Q000032:analysis / Q000096:biosynthesis; D019787:Linoleic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010071:Oxaloacetates / Q000032:analysis; D010477:Perfusion; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007657:Ketone Bodies; D010071:Oxaloacetates; D010743:Phospholipids; D014280:Triglycerides; D001622:Betaine; D002784:Cholesterol; C045761:emeriamine; D019787:Linoleic Acid; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine; D020155:3-Hydroxybutyric Acid