Masayumi Saeki

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 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.

Pentaerythritol tetranicotinate (niceritrol) decreases plasma lipoprotein(a) levels

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

Identification of a functional receptor differing from the LDL receptor that catabolizes chylomicron remnant in Hep G2 cells

We investigated types of lipoprotein receptors on Hep G2 cells using a monoclonal antibody against the LDL receptor. IgG-C7 inhibited the binding and internalization of 125I-labeled low density lipoprotein (LDL) in Hep G2 cells with upregulated and downregulated LDL receptors by 90% of control values. Binding and internalization of 125I-labeled chylomicron remnant in Hep G2 cells with upregulated and downregulated LDL receptors was 50% and 85%, respectively, of control values after exposure to IgG-C7. Excess unlabeled chylomicron remnant inhibited binding and internalization of 125I-labeled chylomicron remnant in Hep G2 cells with downregulated LDL receptors completely. Pronase treatment abolished binding and internalization of 125I-labeled LDL and 125I-labeled chylomicron remnant in Hep G2 cells. When solubilized fractions of Hep G2 cells were immunoprecipitated with IgG-C7, the binding activity of 125I-labeled chylomicron remnant to reconstituted vesicles was unchanged. 45Ca blotting analysis showed the presence of 45Ca binding protein (approximately 600 kDa) in Hep G2 cells. The amount of 45Ca binding protein was not affected by cholesterol and was abolished by pronase treatment. These results suggest the existence of a functional receptor other than the LDL receptor that catabolizes chylomicron remnant in Hep G2 cells and that this receptor may correspond to LDL receptor-related protein.

Deficiency of the basic helix‐loop‐helix transcription factor DEC1 prevents obesity induced by a high‐fat diet in mice

Obesity is a major public health problem in developed countries resulting from increased food intake and decreased energy consumption and usually associated with abnormal lipid metabolism. Here, we show that DEC1, a basic helix‐loop‐helix transcription factor, plays an important role in the regulation of lipid consumption in mouse brown adipose tissue (BAT), which is the major site of thermogenesis. Homozygous Dec1 deletion attenuated high‐fat‐diet‐induced obesity, adipocyte hypertrophy, fat volume and hepatic steatosis. Furthermore, DEC1 deficiency increased body temperature during daytime and enhanced the expression of uncoupler protein 1, a key factor of thermogenesis, and various lipolysis‐related genes in interscapular BAT. In vitro experiments suggested that DEC1 suppresses the expression of various lipolysis‐related genes induced by the heterodimer of peroxisome proliferator‐activated receptor γ and retinoid X receptor α (RXRα) through direct binding to RXRα. These observations suggest that enhanced lipolysis in BAT caused by DEC1 deficiency leads to an increase in lipid consumption, thereby decreasing lipid accumulation in adipose tissues and the liver. Thus, DEC1 may serve as an energy‐saving factor that suppresses lipid consumption, which may be relevant to managing obesity.