Effects of dehydroepiandrosterone on oleic acid accumulation in rat liver.
The purpose of the present study was to determine whether dehydroepiandrosterone (DHEA) affects de novo fatty acid synthesis, oleic acid formation, fatty acid oxidation, and very low density lipoprotein (VLDL) secretion, in relation to the accumulation of lipid containing oleic acid, in rat liver. The rates of hepatic de novo synthesis of both fatty acid and monounsaturated fatty acid, determined by incorporation of 3H from 3H(2)O into fatty acid, were increased markedly when rats were fed a diet containing 0.5% (w/w) DHEA for 14 days. The treatment of rats with DHEA also enhanced the conversion of [14C]stearic acid into oleic acid in the liver in vivo. DHEA did not suppress fatty acid degradation in the liver. Namely, mitochondrial palmitic acid oxidation in liver homogenates and isolated hepatocytes was increased approximately 1.9- and 5-fold, respectively, in DHEA-treated rats. Peroxisomal palmitic acid oxidation in isolated hepatocytes from rats treated with DHEA, however, was not significantly different from that of the control, despite the fact that peroxisomal degradation of palmitic acid in the liver homogenates was increased markedly. The rate of hepatic VLDL secretion in DHEA-treated rats was decreased markedly. These results indicate that the elevation of the hepatic fatty acid content, especially oleic acid, by DHEA feeding is due to an increase in both de novo fatty acid synthesis and the formation of oleic acid and to a decrease in the rate of hepatic VLDL secretion. Mitochondrial and peroxisomal fatty acid degradation does not appear to play a significant role in the accumulation of hepatic lipids.
Imai
Koichi
K
Department of Pharmacy, Saitama Cardiovascular and Respiratory Center, Itai Konan 1696, Osato, 360-0105, Saitama, Japan.
Kudo
Naomi
N
Koyama
Matajiro
M
Kawashima
Yoichi
Y
D000821:Animal Feed; D000818:Animals; D002250:Carbon Radioisotopes; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D019301:Oleic Acid; D019308:Palmitic Acid; D003687:Dehydroepiandrosterone