Yasuhiko Hirata

Effect of dietary hydrogenated corn oil (trans-octadecenoate rich oil) on plasma and hepatic cholesterol metabolism in the hamster.

The effect of dietary hydrogenated corn oil (trans-octadecenoate-rich oil) on plasma cholesterol and triglyceride concentrations was compared with dietary palmitic acid in hamsters given a cholesterol-rich diet. The addition of dietary palmitic acid and hydrogenated corn oil accelerated the increase in plasma VLDL- and LDL-cholesterol levels and plasma triglyceride level induced by dietary cholesterol loading. Dietary cholesterol, palmitic acid and hydrogenated corn oil showed no effect on plasma HDL-cholesterol concentration. A decrease in hepatic LDL receptor activity was seen in animals fed a diet supplemented with cholesterol in combination with palmitic acid or hydrogenated corn oil in comparison with animals fed a diet supplemented with cholesterol alone. Hydrogenated corn oil (trans-octadecenoate-rich oil) appears to potentiate the effect of dietary cholesterol in elevating the plasma VLDL- and LDL-cholesterol levels through the suppression of hepatic LDL receptor activity. trans-Octadecenoate in dietary hydrogenated corn oil may be as atherogenic as dietary palmitic acid due to a suppression of hepatic LDL receptors in the presence of dietary cholesterol loading.

Metabolic changes in lipids of rat plasma and hepatocytes induced by 17α-ethynylestradiol treatment

Cultured hepatocytes isolated from livers of 17 alpha-ethynylestradiol-treated rats were used to investigate the change of lipid metabolism induced by administration of 17 alpha-ethynylestradiol. Treatment with 17 alpha-ethynylestradiol caused a decrease of rat plasma lipids (free cholesterol, cholesterol ester, triacylglycerol and phosphatidylcholine). No difference in the ability of urea nitrogen synthesis could be demonstrated between cultured hepatocytes isolated from livers of 17 alpha-ethynylestradiol-treated rats and propylene glycol-treated rats (control). Total cholesterol and cholesterol ester contents of cultured hepatocytes isolated from livers of 17 alpha-ethynylestradiol-treated rats were increased in comparison with those of the control. Triacylglycerol content of cultured hepatocytes was not affected by 17 alpha-ethynylestradiol treatment. There was no difference in the composition of lipid content between liver tissues and cultured hepatocytes. These results suggest that hepatocytes isolated from livers maintain the character of livers treated with 17 alpha-ethynylestradiol or livers treated with propylene glycol. Free cholesterol and cholesterol ester synthesis from [14C]acetic acid by cultured hepatocytes isolated from livers of 17 alpha-ethynylestradiol-treated rats were decreased to about 30% of the control. Triacylglycerol and polar lipid (phospholipid) synthesis from [14C]acetic acid were not affected by 17 alpha-ethynylestradiol treatment. Microsomal hydroxymethylglutaryl-CoA reductase activity of rat liver treated with 17 alpha-ethynylestradiol was decreased to about 50% of control. The secretions of free cholesterol, cholesterol ester, triacylglycerol, phosphatidylcholine, apolipoprotein BL and BS by cultured hepatocytes isolated from livers of 17 alpha-ethynylestradiol treated rats were not decreased when compared with the control. Because lipid and apolipoprotein secretions from cultured hepatocytes treated with 17 alpha-ethynylestradiol were not decreased and cholesterol contents of liver tissues and cultured hepatocytes treated with 17 alpha-ethynylestradiol were increased and hepatic microsomal hydroxymethylglutaryl-CoA reductase activity was decreased by 17 alpha-ethynylestradiol treatment, it is suggested that the liver plays an important role in hypolipidemia induced by 17 alpha-ethynylestradiol by increasing the plasma lipid uptake mediated by an increased amount of lipoprotein receptors of liver membranes.

Metabolic changes in LDL receptors and an appearance of scavenger receptors after phorbol ester-induced differentiation of U937 cells

Metabolic changes in lipoprotein receptors after cell differentiation were investigated using U937 cells, a human tumor cell line with monoblastic characteristics. After inducing the differentiation of U937 cells into monocyte-macrophage-like cells using TPA (12-tetradecanoyl-phorbol-13-acetate), the incorpotation of [14C]oleate into cellular cholesteryl [14C]oleate was increased in comparison with U937 cells when incubated with r-beta VLDL, h-VLDL or h-LDL. A marked down-regulation of LDL receptors was observed in U937 cells upon addition of 25-hydroxycholesterol. However, this down-regulation of LDL receptors was poor in monocyte-macrophage-like cells that had been induced to differentiate from U937 cells with TPA. Acyl coenzyme A:cholesterol acyltransferase activity was increased after TPA-induced differentiation of U-937 cells. The incorporation of [14C]oleate into cellular cholesteryl [14C]oleate was also increased when incubated with acetylated h-LDL in monocyte-macrophage-like cells in comparison with U937 cells. These results suggest that a poor down-regulation of LDL receptors, which is attributable to increased acyl coenzyme A:cholesterol acyltransferase activity, and scavenger receptors are induced and that these metabolic changes in lipoprotein receptors and an increased acyl coenzyme A:cholesterol acyltransferase activity contribute to cholesterol ester accumulation in monocyte-macrophage-like cells.

Analysis of neutral amino acid trasnport systems in the small intestine: A study of brush border membrane vesicles

SummaryTransport of L-proline, L-leucine and L-cysteine was studied in brush border membrane vesicles prepared from guinea pig ileum. Concentrative transport of L-proline, L-leucine and L-cysteine was obtained in the presence of an Na+ gradient from, outside to inside of the vesicles, which indicated contribution of either system A (alanine-preferring) or system ASC (alanine-, serine- and cysteine-preferring) to the transport. When Na+ was replaced by Li+, L-leucine and L-cysteine maintained the same concentrative transport. However, the concentrative transport of L-proline was markedly decreased by Li+-for-Na+ substitution. Strong exchange properties of L-leucine transport via system L (leucine-preferring) was observed with brush border membrane vesicles, in which preloaded L-methionine could be exchanged with labeled L-leucine added outside the vesicles. These results suggest that the small intestine of the guinea pig possesses classical neutral amino acid transport systems such as systems A, ASC and L.

Probucol Promotes Hepatic Uptake of High Density Lipoprotein in Rats

SummaryProbucol significantly reduced high density lipoprotein (HDL)-cholesterol and apolipoprotein AI in rats. Hepatic uptake of radiolabelled human HDL3 increased significantly in vivo and in the isolated perfused rat liver preparation. In vivo, uptake of HDL3 by the adrenal glands also increased significantly. Hepatic cholesterol content in probucol-treated rats tended to increase, whereas newly synthesised cholesterol decreased significantly. The results of the present study suggest that enhanced uptake of HDL is one of the mechanisms of lowering serum HDL with probucol treatment.