Masanobu Sakono

Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets

The effects of dietary bitter melon (Momordica charantia) freeze-dried powder on serum glucose level and lipid parameters of the serum and liver were studied in rats fed diets supplemented with and without cholesterol. Rats were fed the diets for 14 days containing bitter melon freeze-dried powder at the level of 0.5, 1 and 3% without an added dietary cholesterol (experiment I) and those containing bitter melon at the level of 1% with or without 0.5% cholesterol and 0.15% bile acid (experiment II). No adverse effect of dietary bitter melon powder on growth parameters and relative liver weight were noted. Dietary bitter melon resulted in a consistent decrease in serum glucose levels in rats fed cholesterol-free diets, but not in those fed cholesterol-enriched diets, although no dose-response was noted. Addition of cholesterol to the diets as compared to those without added cholesterol caused hypercholesterolemia and fatty liver. Bitter melon had little effect on serum lipid parameters, except for high density lipoprotein (HDL)-cholesterol; HDL-cholesterol levels tended to decrease by dietary cholesterol, while they were consistently elevated by dietary bitter melon both in the presence and absence of dietary cholesterol, indicating an antiatherogenic activity of bitter melon. In addition, bitter melon exhibited a marked reduction in the hepatic total cholesterol and triglyceride levels both in the presence and absence of dietary cholesterol; the reduction of triglyceride levels in the absence of dietary cholesterol was in a dose-dependent manner. These results suggest that bitter melon can be used as a health food.

Effect of taurine on cholesterol metabolism in hamsters: up-regulation of low density lipoprotein (LDL) receptor by taurine.

The effects of taurine on hepatic cholesterol metabolism were investigated in hamsters fed a high-fat diet or normal chow. Two weeks-treatment of taurine at 1% in drinking water prevented high-fat diet-induced increase in cholesterol levels of serum and liver. The decrease in serum cholesterol by taurine was due to decrease in non-HDL cholesterols. A similar tendency was noted in serum and liver cholesterol levels of hamsters fed a normal diet. In hamsters fed a high-fat diet, taurine prevented elevation in hepatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and increased the activity of cholesterol 7alpha-hydroxylase. Taurine also increased cholesterol 7alpha-hydroxylase activity in hamsters fed normal chow. Studies on liver membranes revealed that taurine increased 125I-labeled LDL binding by 52% and 58% in hamsters fed either a normal chow or high-fat diet, respectively. Furthermore, LDL kinetic analysis showed that taurine intake resulted in significant faster plasma LDL fractional catabolic rates (FCR). These results suggest that taurine elevates hepatic LDL receptor and thereby decreases serum cholesterol levels, an event which may be the result of hepatic cholesterol depletion as a consequence of increased bile acid synthesis via enhancement of cholesterol 7alpha-hydroxylase activity. Thus, up-regulation of the LDL receptor and subsequent increase in receptor- mediated LDL turnover may be a key event in the cholesterol-lowering effects of taurine in hamsters.

Inhibitory effect of ethanolamine plasmalogen on iron- and copper-dependent lipid peroxidation.

The effect of ethanolamine plasmalogen (EtnPm) on lipid peroxidation was investigated in liposomal suspension of egg yolk phosphatidylcholine. EtnPm inhibited iron- and copper-dependent peroxidation in the presence of preformed hydroperoxides, although it was not effective for radical initiator mediated lipid peroxidation. EtnPm resulted in complete binding of iron to liposomal lipids, suggesting that EtnPm exerts its inhibitory effect on lipid peroxidation through inhibiting preformed peroxide decomposition by trapping transition metal ions.

Dietary conjugated linoleic acid reciprocally modifies ketogenesis and lipid secretion by the rat liver

The effects of dietary conjugated linoleic acid (CLA) and linoleic acid (LA) on ketone body production and lipid secretion were compared in isolated perfused rat liver. After feeding the 1% CLA diet for 2 wk, the concentration of post-perfused liver cholesterol was significantly reduced by CLA feeding, whereas that of triacylglycerol remained unchanged. Livers from CLA-fed rats produced significantly more ketone bodies; and the ratio of β-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to be consistently higher in the liver perfusate. Conversely, cumulative secretions of triacylglycerol and cholesterol were consistently lower in the livers of rats fed CLA, and the reduction in the latter was statistically significant. Thus dietary CLA appeared to exert its hypolipidemic effect at least in part through an enhanced β-oxidation of fatty acids at the expense of esterification of fatty acid in the liver.

Whey from cultured skim milk decreases serum cholesterol and increases antioxidant enzymes in liver and red blood cells in rats

Abstract The study was carried out to examine the effect of whey from bovine skim milk fermented with bifidobacteria and lactic acid bacteria on plasma cholesterol and antioxidant enzymes in rats. Rats were maintained for 6 wks on a purified diet (reference diet) and on the purified diet supplemented milk whey or whey from cultured skim milk with Bifidobacterium longum (B. longum), Lactobacillus acidophilus (L. acidophilus) or Streptococcus salivarius subsp. thermophilus (S. thermophilus) . Diets containing the product with S. thermophilus resulted in the lowest concentration of plasma cholesterol. The activity of superoxide dismutase (SOD) in red blood cells (RBC) and the activity of catalase in liver were elevated on cultured product-diets compared with the reference diet; in addition, the activity of glutathione peroxidase (GSHPx) in RBC was higher on the L. acidophilus diet compared with the reference diet. Although there were no significant differences in the concentrations of thiobarbituric acid-reactive substances and α-tocopherol in plasma, plasma d B. longum - and L. acidophilus -diets were resistant to the oxidative stress induced by a transition metal ion when compared with those from rats fed on the reference diet. The non-fermented whey diet was not as effective in lowering plasma cholesterol and in increasing antioxidant enzymes as were the fermentation product diets. These results therefore suggest that wheys from cultured milk may exert spesific effects on hypercholesterolemia and oxidative stress.

Effect of phosphatidylethanolamine and its constituent base on the metabolism of linoleic acid in rat liver

Dietary phosphatidylethanolamine (PE) contributes the circulatory and hepatic free-ethanolamine in rats (Ikeda et al. (1987) Biochim. Biophys. Acta 921, 245). A role for circulatory ethanolamine has not been defined; however, our recent studies have shown that exogenous ethanolamine influences cholesterol and linoleic acid metabolism in rats (Imaizumi et al. (1983) J. Nutr. 113, 2403). In order to understand the role of dietary PE the effects of PE and its base on the hepatic metabolism of linoleic acid were investigated in vivo and in primary cultured hepatocytes in rats. Dietary PE increased the plasmic level of ethanolamine from 37 to 52 microM and decreased the ratio of arachidonate to linoleate in hepatic phospholipids. Activity of hepatic delta 6-desaturase decreased in rats given PE and the desaturation of [14C]linoleate in the cultured hepatocytes decreased by the addition of ethanolamine. Secretion [14C]linoleate labeled very-low-density lipoprotein from the cultured hepatocytes decreased by the addition of ethanolamine. Dietary PE caused an increased formation of CO2 from [14C]acetate by liver slices, and ethanolamine added to the hepatocytes caused an increased oxidation of [14C]linoleate and a suppression of fatty acid synthesis from [3H]serine. These results suggest that ethanolamine derived from the dietary PE plays a regulatory role in the linoleate metabolism in the liver.

Effects of Dietary Soybean Peptides on Hepatic Production of Ketone Bodies and Secretion of Triglyceride by Perfused Rat Liver

Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution.

Dietary Taurine Decreases Hepatic Secretion of Cholesterol Ester in Rats Fed a High-Cholesterol Diet

The effects of dietary taurine on lipid secretion and ketone body production were examined in the livers of Wistar and Sprague-Dawley rats fed high-cholesterol diets. The weight gain of the Sprague-Dawley rats tended to be higher than that of the Wistar rats, although food intake was comparable between the strains. The concentration of hepatic triglyceride was significantly higher but that of phospholipid was significantly lower in the Sprague-Dawley rats. Ketone body production by livers of Sprague-Dawley rats was significantly higher than that by the livers of Wistar rats. Dietary taurine repressed the weight gain of Wistar rats, perhaps due to decreased food intake, but it had no apparent effect on these growth parameters in Sprague-Dawley rats. There was a significant reduction in the hepatic concentration of cholesterol ester, but not other lipid components following feeding of taurine. Taurine feeding resulted in a stimulation of hepatic ketogenesis, whereas it markedly reduced the hepatic secretion of cholesterol ester in both strains of rats. The effect of dietary taurine on the hepatic secretion of triglyceride, phospholipid and free-cholesterol was marginal in either strain. These results suggest that taurine feeding significantly ameliorated the dietary cholesterol-dependent increase in hepatic accumulation and secretion of cholesterol ester, regardless of strain differences, and the decrease in the hepatic secretion of this cholesterol ester appeared to be partly responsible for the observed reduction in the concentration of serum cholesterol following feeding of taurine in these cholesterol-fed rats.

EFFECT OF NK-104, A NEW SYNTHETIC HMG-COA REDUCTASE INHIBITOR, ON TRIGLYCERIDE SECRETION AND FATTY ACID OXIDATION IN RAT LIVER

For the investigation of the mechanism responsible for the hypotriglyceridemic effect of NK-104, a new synthetic inhibitor of HMG-CoA reductase, the rate-limiting enzyme for cholesterol synthesis, isolated rat liver was perfused with or without NK-104 in the presence of exogenous [1-(14)C]oleic acid substrate. Addition of NK-104 tended to increase the ketone body production while it caused a significant decrease in the secretion rate of triglyceride by the perfused liver without affecting uptake of exogenous [1-(14)C]oleic acid. The inhibitor also significantly decreased hepatic triglyceride concentration. The altered triglyceride secretion was accompanied by a concomitant decreased incorporation of exogenous [1-(14)C]oleate into triglyceride. The conversion of exogenous [1-(14)C]oleic acid substrate indicated an inverse relationship between the pathways of oxidation and esterification. No effect of NK-104 on hepatic secretion of cholesterol was observed. These results suggest that NK-104 exerts its hypotriglyceridemic action, primarily by diverting the exogenous free fatty acid to the pathways of oxidation at the expense of esterification.

GEMFIBROZIL REDUCES NON-HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN EXOGENOUSLY HYPERCHOLESTEROLEMIC (EXHC) RATS FED A HIGH-CHOLESTEROL DIET

Gemfibrozil is a widely used drug prescribed to elevate serum high-density lipoprotein (HDL) cholesterol levels and lower triacylglycerols. The present study was done to determine if the drug would alleviate hypercholesterolemia in exogenously hypercholesterolemic (ExHC) rats. In the drug-treated ExHC rats, the serum non-HDL cholesterol levels were lowered and the ratio of the non HDL cholesterol to serum triacylglycerols was decreased to the extent seen in the drug-treated SD rats. Liver cholesterol and triacylglycerols were lowered in the drug-treated rats. There was also an increase in fecal excretion of neutral sterols and bile acids, particularly chenodeoxycholic and beta-muricholic acids. The drug elevated cholesterol 7 alpha-hydroxylase activity and mRNA abundance and acyl-CoA cholesterol acyltransferase activity in the liver, but did not influence low-density lipoprotein receptor mRNA level in the liver. Thus, gemfibrozil is effective in alleviating hypercholesterolemia in exogenously hypercholesterolemic rats, by partitioning hepatic cholesterol into biliary excretion.