Hiromasa Ohtani

Opposite effects on cholesterol metabolism and their mechanisms induced by dietary oleic acid and palmitic acid in hamsters

The effects of dietary oleic acid on cholesterol metabolism were investigated and compared with those of palmitic acid in hamsters. Addition of 5% oleic acid to a 0.1% cholesterol-supplemented diet decreased plasma total cholesterol, very low density lipoprotein (VLDL) cholesterol, and low density lipoprotein (LDL) cholesterol, increased hepatic LDL receptor activity, and decreased plasma cholesteryl ester transfer protein (CETP) activity in comparison with 0.1% cholesterol alone. In contrast, addition of 5% palmitic acid to a 0.1% cholesterol-supplemented diet increased total cholesterol and LDL-cholesterol, increased plasma CETP activity, and suppressed hepatic LDL receptor activity to a greater extent than 0.1% cholesterol alone. Neither oleic acid nor palmitic acid altered hepatic microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, but oleic acid increased hepatic microsomal cholesterol 7 alpha-hydroxylase activity. These results suggest that dietary oleic acid inhibits the increases in total, VLDL-, and LDL-cholesterol induced by dietary cholesterol by preventing both LDL receptor suppression and increased CETP activity, whereas dietary palmitic acid augments the cholesterol-induced increases in total and LDL-cholesterol by both further suppression of LDL receptor activity and further stimulation of CETP activity.

DECREASES IN PLASMA LIPID CONTENT AND THROMBOTIC ACTIVITY BY ETHYL ICOSAPENTATE PURIFIED FROM FISH OILS

Abstract The effects of ethyl icosapentate (purified from fish oils) on plasma lipids, activity of coagulation factors VII and X, and content of plasminogen activator inhibitor-1 were examined in 28 patients with familial combined hyperlipidemia. After 8 weeks, ethyl icosapentate at 1800 mg daily significantly decreased plasma total cholesterol and triglyceride levels, activity of coagulation factors VII and X, and content of plasminogen activator inhibitor-1 without deleterious effects on plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and plasma apolipoproteins. Activity of coagulation factors VII and X and the content of plasminogen activator inhibitor-1 correlated with triglyceride levels at week 0 while only coagulation factor VII correlated with total cholesterol at week 0. Changes in coagulation factor activity and content of plasminogen activator inhibitor-1 did not correlate with that of plasma total cholesterol or triglyceride after 8 weeks. Purified ethyl icosapentate would thus appear to have an antiatherogenic effect and could be essential in the control of coronary heart disease by lowering plasma lipid content and increasing antithrombotic action.

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.

Hypolipidemic effect of beraprost sodium in patients with arteriosclerosis obliterans accompanied by hyperlipidemia

Abstract The effect of beraprost sodium, a stable prostaglandin I 2 analog, on plasma lipids and apolipoproteins was examined in 18 patients with arteriosclerosis obliterans (Fontaine I) accompanied by hyperlipidemia. Twelve weeks of therapy with beraprost sodium at 120 μg daily significantly decreased plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels without a deleterious effect on plasma triglyceride, high-density lipoprotein (HDL) cholesterol, or apolipoprotein levels. A positive correlation was observed between the change in plasma total cholesterol and that in plasma LDL cholesterol due to the administration of beraprost sodium. Although this is a preliminary study, the results suggest beraprost sodium exerts an antiatherogenic effect. By lowering plasma total cholesterol and LDL cholesterol levels, beraprost sodium may prove to be important in the control of arteriosclerosis obliterans with hyperlipidemia.

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.

Amino Acid Transport System of the Guinea Pig Small Intestine is Injured by Hydroxyl Radicals

The mechanism for the damage to the alanine-preferring amino acid transport system (A system) of guinea pig intestinal brush border membrane vesicles induced by active oxygen species was studied in vitro. The transport activity of L-proline, which is a model amino acid for the A system, and the tryptophan fluorescence intensity of intestinal brush border membrane vesicles were decreased, and lipid peroxidation of these membrane vesicles was induced by ultraviolet irradiation, which generated active oxygen species. Thiourea (hydroxyl radical scavenger) protected L-proline transport activity and tryptophan fluorescence intensity of intestinal brush border membrane vesicles and also inhibited lipid peroxidation in these membrane vesicles in the presence of active oxygen radicals. alpha-Tocopherol (singlet oxygen radical scavenger) inhibited lipid peroxidation of intestinal brush border membrane vesicles but protected neither L-proline transport activity nor tryptophan fluorescence intensity in these membrane vesicles in the presence of active oxygen radicals. Catalase and superoxide dismutase showed no protective effect on L-proline transport activity, tryptophan fluorescence intensity, or lipid peroxide formation in intestinal brush border membrane vesicles in the presence of active oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypolipidemic effect of saiko-ka-ryukotsu-borei-to (TJ-12) in patients with type II or type IV hyperlipidemia

Abstract This open-label, uncontrolled trial evaluated the effect of Kampo medicine. Saiko-ka-ryukotsu-borei-to (TJ-12), on plasma lipids and apolipoproteins in 21 patients (3 men and 18 women) with type II or type IV hyperlipidemia. The mean age of the patients was 60.2 ± 7.2 years and the mean weight was 55.9 ± 9.4 kg. Twelve weeks after daily administration of 7.5 g of TJ-12, total cholesterol levels, low-density lipoprotein (LDL)-cholesterol levels, and the atherogenic index (defined as the difference between total cholesterol levels and high-density lipoprotein [HDL]-cholesterol levels divided by HDL-cholesterol levels) were significantly decreased (pretreatment vs posttreatment mean value, 263 ± 31 mg/dL vs 239 ± 36 mg/dL, 177 ± 39 mg/dL vs 163 ± 35 mg/dL, and 4.3 ± 8.9 mg/dL vs 3.8 ± 8.7 mg/DL, respectively). There was a significant positive correlation between the change in total cholesterol levels and that in LDL-cholesterol levels. These results suggest that TJ-12 might diminish atherogenesis by reducing the plasma levels of total cholesterol and LDL-cholesterol.