Kimio Sugiyama

Eritadenine-induced alteration of hepatic phospholipid metabolism in relation to its hypocholesterolemic action in rats

Abstract The hypocholesterolemic effect of dietary supplementation with eritadenine, a hypocholesterolemic factor present in the Lentinus edodes mushroom, was investigated in relation to its effect on hepatic phospholipid metabolism in rats. The plasma total cholesterol level was significantly decreased by eritadenine supplementation at levels above 8 μmol/kg of diet in a dose-dependent manner, accompanying decreases in both VLDL + LDL and HDL cholesterol levels. Eritadenine supplementation significantly increased the phosphatidylethanolamine (PE) content and inversely decreased the phosphatidylcholine (PC) content of liver microsomes in a dose-dependent manner. There was a highly significant correlation between plasma cholesterol levels and the content or proportion of PC and PE of liver microsomes. Eritadenine supplementation did not decrease the activity of PE N-methyltransferase in liver microsomes but rather increased the activity, possibly because of the increased PE content of liver microsomes. On the one hand, eritadenine had no direct inhibitory effect on the enzyme activity when added to the assay mixture. On the other hand, eritadenine supplementation increased the hepatic S-adenosylhomocysteine (SAH) level and decreased the ratio of S-adenosylmethionine (SAM) to SAH in a dose-dependent manner. The in vivo incorporation of radioactivity of [methyl-3H]methionine into the PC of liver microsomes and blood plasma was also markedly depressed by dietary eritadenine supplementation at a level of 200 μmol/kg of diet. These results suggest that the hypocholesterolemic action of eritadenine might be elicited through an alteration of the hepatic phospholipid metabolism that resulted from an inhibition of PE N-methylation due to a decreased SAM SAH ratio in the liver.

Amino acid composition of dietary proteins affects plasma cholesterol concentration through alteration of hepatic phospholipid metabolism in rats fed a cholesterol-free diet

Abstract This study was designed to investigate the relationship between the amino acid composition of dietary proteins and the plasma cholesterol concentration and to examine whether the alteration of hepatic phospholipid metabolism participates in the effect of dietary proteins in rats fed a cholesterol-free diet. There was a significant positive correlation between the plasma total cholesterol concentration and the plasma concentration of methionine and valine and the hepatic concentration of valine and alanine in rats fed seven types of proteins. In contrast, the plasma cholesterol concentration exhibited a significant negative correlation with the hepatic-free ethanolamine concentration. As far as methionine and ethanolamine, their positive and negative correlation with the plasma cholesterol concentration was consistent with their known hyper- and hypocholesterolemic effects, respectively. The phospholipid profile as represented by the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver microsomes, but not in other tissues tested, was largely influenced by the type of dietary proteins; the PC PE ratio exhibited a significant positive correlation with the plasma total cholesterol concentration. There was a significant correlation between the methionine content of dietary proteins and several biochemical variables including plasma cholesterol and liver microsomal PC PE ratio. A significantly lower concentration of hepatic S-adenosylmethionine was observed with soybean protein diet than with casein diet suggesting a decrease in the PC biosynthesis via the PE N-methylation pathway in rats fed soybean protein. From these results, it is suggested that the plasma cholesterol concentration might be influenced by the methionine content of dietary proteins at least in part through an alteration of hepatic phospholipid metabolism.

Suppression of Methionine-Induced Hyperhomocysteinemia by Glycine and Serine in Rats

The hyperhomocysteinemia induced by a dietary addition of 1% methionine was significantly suppressed by the concurrent addition of 1% glycine or 1.4% serine to the same degree. The methionine-induced increase in the hepatic concentration of methionine metabolites was significantly suppressed by glycine and serine, but the hepatic cystathionine β-synthase activity was not enhanced by these amino acids. When the methionine-supplemented diet was changed to the methionine plus glycine or serine diet, the plasma homocysteine concentration rapidly decreased during and after the first day. The hyperhomocysteinemia induced by an intraperitoneal injection with methionine was also suppressed by concurrent injection with glycine or serine, although the effect of serine was significantly greater than that of glycine. These results indicate that glycine and serine were effective for suppressing methionine-induced hyperhomocysteinemia: serine and its precursor glycine are considered to have elicited their effects mainly by stimulating cystathionine synthesis by supplying serine, another substrate for cystathionine synthesis.

Dietary Resistant Starch Alters the Characteristics of Colonic Mucosa and Exerts a Protective Effect on Trinitrobenzene Sulfonic Acid-induced Colitis in Rats

The protective effect of a dietary high-amylose cornstarch (HAS) against trinitrobenzene sulfonic acid (TNBS)-induced colitis was examined in rats. Rats were fed a HAS-free basal diet or, a 15% or 30% HAS supplemented diet for 10 d, and then received intracolonic TNBS to induce colitis and fed the respective diets for a further 8 d. HAS ingestion significantly protected colonic injuries as evidenced by lower colonic myeloperoxidase activity. Rats fed the HAS diet showed greater cecal short-chain fatty acid (SCFA) production than those fed the basal diet. Further, just before TNBS administration, HAS ingestion dose-dependently increased fecal and cecal mucin contents, and protein and nucleic acid contents in the colonic mucosa. HAS ingestion also reduced colonic permeability. The protective effect of HAS ingestion on TNBS-induced colitis is perhaps exerted through alterations in colonic mucosa, possibly due to cecal SCFA production.

Dietary eritadenine-induced alteration of molecular species composition of phospholipids in rats

The effect of dietary eritadenine, a hypocholesterolemic compound found in the mushroomLentinus edodes, on the fatty acid and molecular species profiles of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver microsomes was investigated in relation to the hypocholesterolemic action of the compound in rats. Animals were fed the control or eritadenine-supplemented (50 mg/kg diet) diet for 14 d. Eritadenine supplementation significantly decreased the plasma concentrations of cholesterol and phospholipids, but not triglycerides. The PC/PE ratio of liver microsomes, but not plasma, was also markedly decreased by eritadenine. Eritadenine supplementation was found to increase the proportion of 18:2n-6 and, inversely, to decrease the proportion of 20:4n-6 and 22:5n-6 in plasma PC and liver microsomal PC and PE, indicating that eritadenine depressed the metabolism of linoleic acid. The effect of eritadenine on the profile of n-3 fatty acids was dissimilar in PC and PE. These changes in fatty acid composition were selectively reflected in the molecular species composition of both PC and PE; the extent of increase in 16:0–18:2 molecular species or decrease in 18:0–20:4 molecular species was apparently greater than that of other molecular species containing 18:2 or 20:4 in the sn-2 position. These results suggest that, in addition to the decrease in liver microsomal PC/PE ratio, the alteration of plasma PC molecular species composition might also participate in the hypocholesterolemic action of eritadenine.

Ingestion of resistant starch protects endotoxin influx from the intestinal tract and reduces D‐galactosamine‐induced liver injury in rats

Background and Aims:  The aim of the present study was to examine the protective effect of a dietary high‐amylose cornstarch (HAS) against D‐galactosamine (D‐GalN)‐induced liver injury, focusing specifically on intestinal endotoxin translocation.

Dietary Indigestible Components Exert Different Regional Effects on Luminal Mucin Secretion through Their Bulk-Forming Property and Fermentability

The purpose of this study was to examine the effects of dietary indigestible components on mucin secretion in the respective parts of the gastrointestinal tract through their physico-chemical properties. Rats were fed either a control diet or diets containing 5% polystyrene foam (PSF), 5% fructooligosaccharide (FOS), 5% PSF + 5% FOS, or 10% beet fiber for 10 d. Mucins in the small intestine and feces were greater in the PSF, PSF + FOS, and beet fiber groups than in the control and FOS groups. In the cecum, greater mucins were observed in the FOS, PSF + FOS, and beet fiber groups than in the control and PSF groups. None of the dietary treatment was effective on gastric mucins. Cecal mucins were significantly correlated with the cecal pool sizes of total short-chain fatty acids. The correlation between fecal mucins and fecal numbers was also significant. The results suggest that the effect of the bulk-forming property of the dietary indigestible component on mucin secretion is limited to the duct, while fermentability is effective only in the cecum.

Eritadenine-induced Alterations of Plasma Lipoprotein Lipid Concentrations and Phosphatidylcholine Molecular Species Profile in Rats Fed Cholesterol-free and Cholesterol-enriched Diets

The effects of dietary eritadenine on the concentration of plasma lipoprotein lipids and the molecular species profile of plasma lipoprotein phosphatidylcholine (PC) were investigated in rats fed cholesterol-free and cholesterol-enriched diets to obtain insights into the relationship between the changes in PC molecular species profile and the hypocholesterolemic action of eritadenine. The effect of eritadenine on the secretion rate of very low density lipoprotein (VLDL) from the liver was also estimated. Rats were fed the control or eritadenine-supplemented (50 mg/kg) diets with or without exogenous cholesterol for 14 d. Eritadenine supplementation significantly decreased the cholesterol of major plasma lipoproteins, high density lipoprotein and VLDL, in rats fed cholesterol-free and cholesterol-enriched diets, respectively. The ratio of PC to phosphatidylethanolamine, Δ6-desaturase activity, and the ratio of arachidonic acid to linoleic acid in liver microsomes were markedly decreased by eritadenine irrespective of the presence or absence of exogenous cholesterol. Dietary eritadenine increased the proportion of 16:0-18:2 molecular species with a decrease in 18:0-20:4 in plasma lipoprotein PC in both rats fed cholesterol-free and cholesterol-enriched diets. Eritadenine did not depress the secretion rate of VLDL in rats fed a cholesterol-free diet containing a high level of choline. The results indicate that dietary eritadenine elicits its hypocholesterolemic action with modulations of the fatty acid and molecular species profiles of PC irrespective of the presence or absence of exogenous cholesterol. The eritadenine-induced alteration of PC molcular species profile is discussed in relation to the hypocholesterolemic action of eritadenine.

Dietary methionine level affects linoleic acid metabolism through phosphatidylethanolamine N-methylation in rats.

The effects of dietary methionine level on the profiles of fatty acids and phospholipids and on the plasma cholesterol concentration were investigated to confirm whether the methionine content of dietary proteins is one of the major factors that cause differential effects on lipid metabolism. The effect of dietary supplementation with eritadenine, which is shown to be a potent inhibitor of phosphatidylethanolamine (PE) N-methylation, was also investigated. Rats were fed six diets containing casein (100 g/kg) and amino acid mixture (86.4 g/kg) differing in methionine content (2.5, 4.5, and 7.5 g/kg) and without or with eritadenine supplementation (30 mg/kg) for 14 d. The ratio of arachidonic to linoleic acid of liver microsomal and plasma phosphatidylcholine (PC) was significantly increased as the methionine level of diet was elevated, indicating that dietary methionine stimulates the metabolism of linoleic acid. The PC/PE ratio of liver microsomes and the plasma cholesterol concentration were also increased by dietary methionine. These effects of methionine were completely abolished by eritadenine supplementation The S-adenosylmethionine concentration in the liver reflected the methionine level of diet. These results support the idea that the differential effects of dietary proteins on lipid metabolism might be ascribed, at least in part, to their different methionine contents, and that methionine might exert its effects through alteration of PE N-methylation.

Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats

Rats were fed 25% casein (25C) diets differing in choline levels (0–0.5%) with and without 0.5% guanidinoacetic acid (GAA) or 0.75% L-methionine for 7 d to determine the effects of dietary choline level on experimental hyperhomocysteinemia. The effects of dietary choline (0.30%) and betaine (0.34%) on GAA- and methionine-induced hyperhomocysteinemia were also compared. Dietary choline suppressed hyperhomocysteinemia induced by GAA, but not by methionine, in a dose-dependent manner. GAA-induced enhancement of the plasma homocysteine concentration was suppressed by choline and betaine to the same degree, but the effects of these compounds were relatively small on methionine-induced hyperhomocysteinemia. Dietary supplementation with choline and betaine significantly increased the hepatic betaine concentration in rats fed a GAA diet, but not in rats fed a methionine diet. These results indicate that choline and betaine are effective at relatively low levels in reducing plasma homocysteine, especially under the condition of betaine deficiency without a loading of homocysteine precursor.