Biomedical subjects

N Iritani

Publications and source records attributed to N Iritani.

At least 55 records · Page 3Linked to original sources

PubMed1989

Effects of insulin and fructose on transcriptional and post-transcriptional regulation of malic enzyme synthesis in diabetic rat liver.

Insulin action on regulation of hepatic malic enzyme has been investigated in comparison with fructose, using streptozotocin-induced diabetic rats. Insulin-treatment caused a 2.8-fold increase in the transcriptional rate of malic enzyme (EC 1.1.1.40) after 8 h, and a 5-fold increase in the mRNA concentration of the liver. In Northern blot analysis, we demonstrated that after insulin treatment, the nuclear mRNA of malic enzyme tended to increase more rapidly than the total cellular mRNA. Therefore, it is suggested that the nuclear mRNA was primarily increased by insulin. The insulin-dependent increase of malic enzyme mRNA was blocked by cycloheximide, suggesting that synthesis of a peptide is required. On the other hand, by feeding a high-fructose diet to diabetic rats, the malic enzyme mRNA concentration was considerably increased, though with a delayed peaking in comparison with the insulin-treated animals, whereas the transcriptional rate was not significantly increased. Dietary fructose may stabilize the transcripts. Fructose increased the enzyme level far less than the mRNA level. These results suggest that insulin is required in both the translational and transcriptional regulation of malic enzyme.

Animals↗

PubMed1988

Effects of corn oil- and fish oil-supplemented diets on phospholipid fatty acid composition of rat liver nuclei.

The effects of dietary fat on fatty acid compositions of phospholipids in liver nuclei were investigated. By feeding a diet containing 5% corn oil or fish oil to rats, the proportions of n -6 or n -3 polyunsaturated fatty acids (PUFA), respectively, were increased in phospholipids of the liver nuclei. By feeding a fat-free diet, endogenous PUFA were increased. Even after feeding the fat-free diet for 40 weeks, the n - 6 still remained at about 10% in both phosphatidylcholine (PC) and phosphatidylethanolamine (PE), while the n -3 PUFA remained at about 5 and 16% in PC and PE, respectively. The fatty acid compositions of phospholipids in the liver nuclei were influenced by dietary fat and were roughly similar to those in the microsomes. The proportion of n - 3 PUFA was high in PE of both the nuclear membrane and matrix. The proportion of n - 6 was higher in both PC and PE of the nuclear matrix than in those of the membrane.

Animals↗

PubMed1988

Transcriptional and posttranscriptional regulation of malic enzyme synthesis by insulin and triiodothyronine.

To investigate the transcriptional and posttranscriptional regulation of malate dehydrogenase (EC 1.1.1.40) induction by insulin, the transcriptional rate, mRNA concentration and enzyme induction of malic enzyme were compared in livers of normal and diabetic rats fed a high-carbohydrate diet. When rats were fed the diet for 4 days, the enzyme induction and mRNA concentration in livers of diabetic rats were only about 10% and 39%, respectively, of the values of normal rats, and the transcriptional rate was about 64%. Insulin treatment restored the transcriptional rate and mRNA concentration in 8 h and the enzyme induction in 4 days. Thus, it is suggested that insulin is involved in malic enzyme transcription of the gene and also possibly in the translation of the cytoplasm. On the other hand, by giving triiodothyronine treatment, the transcriptional rate and mRNA concentration were increased about twice and the enzyme induction, about 10-times in the diabetic animals. Triiodothyronine appears to stimulate malic enzyme transcription and possibly post-transcriptional steps even at a very low insulin level.

Animals↗

PubMed1988

Lipogenic enzyme induction and incorporation of exogenous fatty acid into liver and liver nuclei.

The incorporation of exogenous fatty acid into lipids of liver and liver nuclei of rats fed diets with or without fat was compared. When [3H]palmitic acid was injected into rats, more radioactivity was incorporated into triacylglycerols and phospholipids of liver and liver nuclei from rats fed the fat-free diet than from those fed the fat diet. The results were supported further by an autoradiographic study. On the other hand, the enzyme induction and quantity of malic enzyme mRNA were decreased by fat feeding. Other lipogenic enzymes were also coordinately decreased. Thus, it may be possible that exogenous fatty acid is involved in nuclear regulation in addition to cytosolic regulation of lipogenic enzyme induction.

Animals↗

PubMed1988

Effects of dietary casein and soybean protein on triglyceride turnover in rat liver.

We previously found that hepatic lipogenic enzyme induction, fatty acid synthesis, and triglyceride level were markedly lower in rats fed soybean protein than in those fed casein (Iritani et al. (1986): J. Nutr., 116: 190). After labeling triglycerides with tritiated water, the effects of dietary protein on the triglyceride degradation have been investigated. After the injection of tritiated water into rats, the radioactivities of fatty acids and triglycerides reached a plateau in 1-2 days and were markedly lower in the soybean protein group than in the casein group. The decreasing rates of triglyceride radioactivities were similar between the casein and soybean protein groups. The enzyme activities in glycerolipid synthesis were similar between the groups. Therefore, the lowering effects of soybean protein on triglyceride levels appear to be ascribed to triglyceride synthesis (due to fatty acid synthesis) rather than to the degradation.

Animals↗

PubMed1987

Influence of diet on the transcriptional and post-transcriptional regulation of malic enzyme induction in the rat liver.

Fasted rats were refed a carbohydrate/protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate) to investigate, using a cDNA cloned in our laboratory, the regulatory mechanisms involved in hepatic malic enzyme induction. In the carbohydrate/protein diet, although the enzyme activity and the mRNA concentration of malic enzyme were increased about 7-fold above the levels in the fasted rat, the rate of transcription was increased only 2-fold. In the carbohydrate diet group the rate of transcription and the concentration of mRNA were increased to the levels in the carbohydrate/protein diet group, whereas the enzyme activity increased only to 60% of those levels. Protein appears to contribute to an increase in the translation of malic enzyme mRNA. In the protein diet group the transcriptional rate was not low, but the mRNA concentration was about half in comparison with the level of the carbohydrate/protein diet group. Further, dietary fat did not reduce the transcriptional activity, but reduced the mRNA concentration and the enzyme activity to half of the basal levels. Therefore, it is suggested that fat stimulates the degradation of the mRNA in liver cytosol, whereas carbohydrate tends to stabilize the mRNA. On the other hand 3,5,3'-triiodothyronine treatment increased the transcriptional activity by 1.5-2-fold above the basal values on all the diets and even on fasting. Thus, it is suggested that 3,5,3'-triiodothyronine increases the transcriptional activity of malic enzyme independently from nutritional regulation, while the nutrients are predominantly involved in the post-transcriptional steps.

Animals↗

PubMed1987

Effects of aging on contributions of dietary fat and triiodothyronine treatment to lipogenic enzyme induction.

Although lipogenic enzyme inductions are reduced by fat feeding, this reduction decreases with aging and is particularly detectable in the case of acetyl-CoA carboxylase and fatty acid synthetase activities. On the other hand, the fat-dependent reductions of malic enzyme and acetyl-CoA carboxylase were consistently relieved by triiodothyronine (T3) treatment. The effects of T3 treatment on these enzyme inductions were greater in 10-month-old rats than in 1-month-old rats, while the carbohydrate-dependent induction and the fat-dependent reduction of the enzymes decreased with aging. In these animals, alterations in malic enzyme mRNA translational activities were roughly in parallel to the enzyme activities. Therefore, the age-dependent alterations in effects of T3 treatment and fat on malic enzyme induction do not appear to occur in post-translation.

Acetyl-CoA Carboxylase↗

PubMed1987

Effects of amino-acid composition of the medium and addition of fatty-acid derivatives on the induction of lipogenic enzymes in cultured hepatocytes.

Effects of essential and non-essential amino acids on induction of lipogenic enzymes were investigated in cultured rat hepatocytes. Glucose-6-phosphate dehydrogenase was markedly induced by the addition of essential amino acids alone to the cultured medium, but was not induced by non-essential amino acids. Fatty-acid synthetase was also markedly induced by a combination of both amino-acid types (more than by either type of amino acid alone). However, acetyl-CoA carboxylase and malic enzyme were slightly induced by the addition of essential and/or non-essential amino acids. When various kinds of fatty acids were individually added to the medium, the lipid-dependent decreases in lipogenic enzyme inductions were in the following order: 18:2 greater than 20:4 greater than 18:1 greater than 16:0. When either linoleic acid, linoleoyl-CoA or trilinolein was added to the medium, linoleic acid was more effective as an inhibitor of the induction, without impairing the viability of cells.

Acetyl-CoA Carboxylase↗

PubMed1987

Asymmetric distribution of arachidonic and n-3 polyunsaturated fatty acids in rat liver microsomal membranes under a fat-free diet.

Rats adapted to a corn oil or a fish oil diet were fed a fat-free diet, and changes in phospholipid polyunsaturated fatty acids (PUFA) in the inner and outer leaflets of liver microsomal membranes were followed for 18 wk. In rats previously adapted to a corn oil diet, arachidonic acid in phosphatidylcholine and phosphatidylethanolamine in the inner and outer leaflets did not decrease quickly; rather, linoleic acid decreased more than arachidonic acid for the first three weeks of feeding the fat-free diet. Even at 18 wk, 40-50% of the beginning arachidonic acid levels were still retained. In contrast, in rats previously adapted to a fish oil diet, the n-3 PUFA were quickly decreased by the fat-free diet to only 10-30% at 18 wk. Due to the appearance and increase of n-9 eicosatrienoic acid in the replacement of the n-3 and n-6 PUFA, total PUFA did not decrease in the inner and outer phosphatidylcholine in either group, but decreased somewhat in the phosphatidylethanolamine due to the insufficient increase of the n-9. On the other hand, the overall degrees of unsaturation in phosphatidylcholine fatty acids were always higher in the outer than in the inner leaflets and were not altered by feeding the fat-free diet even for 18 wk. Thus, the results appear to reveal the physiological importance of unsaturation ratio of fatty acids and the necessity of arachidonic acid in each membrane leaflet.

Animals↗

PubMed1986

Effects of dietary nutrients on substrate and effector levels of lipogenic enzymes, and lipogenesis from tritiated water in rat liver.

When fasted rats were refed for 4 days with a carbohydrate and protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate), the effects of dietary nutrients on the fatty acid synthesis from injected tritiated water, the substrate and effector levels of lipogenic enzymes and the enzyme activities were compared in the livers. In the carbohydrate diet group, although acetyl-CoA carboxylase was much induced and citrate was much increased, the activity of acetyl-CoA carboxylase extracted with phosphatase inhibitor and activated with 0.5 mM citrate was low in comparison to the carbohydrate and protein diet group. The physiological activity of acetyl-CoA carboxylase seems to be low. In the protein diet group, the concentrations of glucose 6-phosphate, acetyl-CoA and malonyl-CoA were markedly higher than in the carbohydrate and protein group, whereas the concentrations of oxaloacetate and citrate were lower. The levels of hepatic cAMP and plasma glucagon were high. The activities of acetyl-CoA carboxylase and also fatty acid synthetase were low in the protein group. By feeding fat, the citrate level was not decreased as much as the lipogenic enzyme inductions. Comparing the substrate and effector levels with the Km and Ka values, the activities of acetyl-CoA carboxylase and fatty acid synthetase could be limited by the levels. The fatty acid synthesis from tritiated water corresponded more closely to the acetyl-CoA carboxylase activity (activated 0.5 mM citrate) than to other lipogenic enzyme activities. On the other hand, neither the activities of glucose-6-phosphate dehydrogenase and malic enzyme (even though markedly lowered by diet) nor the levels of their substrates appeared to limit fatty acid synthesis of any of the dietary groups. Thus, it is suggested that under the dietary nutrient manipulation, acetyl-CoA carboxylase activity would be the first candidate of the rate-limiting factor for fatty acid synthesis with the regulations of the enzyme quantity, the substrate and effector levels and the enzyme modification.

Acetyl Coenzyme A↗

PubMed1986

Effects of dietary nutrients on lipogenic enzyme and mRNA activities in rat liver during induction.

By feeding a carbohydrate diet (without protein) to fasted rats, malic enzyme mRNA activity in the liver was increased to the level in rats fed a carbohydrate and protein diet, whereas the enzyme activity itself was increased to 60% of that level. It appears that malic enzyme mRNA activity was increased by dietary carbohydrate, while dietary protein contributed to an increase in the translation of mRNA. In the animals fed carbohydrate without protein, glucose-6-phosphate dehydrogenase mRNA activity increased to 50% of the level in rats fed the carbohydrate and protein diet, whereas the enzyme activity increased to only 25%. By feeding a protein diet (without carbohydrate), glucose-6-phosphate dehydrogenase activity increased to 65% of the level in rats fed both carbohydrate and protein. This enzyme induction appears to be more dependent on protein than carbohydrate. With the carbohydrate diet, acetyl-CoA carboxylase was induced up to the level in the carbohydrate and protein diet group, whereas fatty acid synthetase was induced to only 33%. Acetyl-CoA carboxylase induction appears to be carbohydrate dependent. On the other hand, isotopic leucine incorporation studies showed that the magnitudes of the enzyme inductions caused by the dietary nutrients should be ascribed to the enzyme synthesis rates rather than the degradation. By fat feeding, the mRNA activities of malic enzyme and glucose-6-phosphate dehydrogenase were markedly decreased along with the enzyme induction. Fat appears to reduce these enzyme inductions before the translation of mRNA.

Acetyl-CoA Carboxylase↗

PubMed1986

Effects of dietary proteins on lipogenic enzymes in rat liver.

When fasted rats were fed fat-free diets containing various sources of protein for 3 d, the activities of liver glucose-6-phosphate dehydrogenase, malic enzyme, acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in rats fed soybean protein or gluten than in those fed casein or fish protein. Since malic enzyme mRNA activity was not low in the soybean protein-fed animals, the translation of malic enzyme appears to be suppressed by dietary soybean protein. The incorporation of tritiated water into liver fatty acids was significantly lower in animals fed soybean protein than in those fed casein. The triglyceride levels in plasma and especially in liver were also lower in the groups fed soybean and gluten than in the groups fed casein and fish. In addition, when dietary soybean protein was replaced with amino acids to simulate casein or soybean protein, the effects on the levels of lipogenic enzymes were still found but were not as great. Thus, some effects can be ascribed to the protein itself and some to the amino acid composition of the diet.

Acetyl-CoA Carboxylase↗

PubMed1986

Heat-inactivation of liver glucose-6-phosphate dehydrogenase and malic enzyme in 1- and 12-month-old rats.

The heat-labilities of liver glucose-6-phosphate dehydrogenase and malic enzyme of 1- and 12-month-old rats were observed by incubation of the crude enzymes at 52 and 55 degrees C, respectively. The biphasic heat-inactivation curves were obtained for those enzymes of the 12-month-olds, whereas no biphasic curves were obtained for the enzymes of the 1-month-olds. The age-dependent rapid inactivations of glucose-6-phosphate dehydrogenase and malic enzyme were not relieved by addition of their substrates in the incubation media. However, the rapid age-dependent inactivations of these enzymes disappeared by addition of NADP. It is suggested that the age-dependent heat-inactivation of these enzymes is ascribed to the conformational modification of the proteins.

Aging↗

PubMed1985

Diurnal variations of lipogenic enzymes, their substrate and effector levels, and lipogenesis from tritiated water in rat liver.

The activities of glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthetase and acetyl-CoA carboxylase (extracted with or without phosphatase inhibitor) in rat liver did not vary significantly during 24 h. The hepatic levels of glucose 6-phosphate and malate increased coordinately 3-6 h after the beginning (1900 h) of food intake and were high until morning, whereas the levels of acetyl-CoA and citrate peaked at 1900 h and then decreased. However, it is remarkable that the in vivo incorporation of 3H from tritiated water into fatty acids in liver increased with the level of malonyl-CoA after food intake. Comparing the substrate and effector levels with the Km and Ka values for the enzymes, the levels of acetyl-CoA, malonyl-CoA and citrate appear to limit the enzyme activities. It is suggested that, after food intake, the physiological activity of acetyl-CoA carboxylase was increased with the substrate increase and/or with the catalytic activation with citrate, and consequently, the fatty acid synthetase activity was also increased, whereas the enzyme activities measured under optimum conditions were not.

Acetyl-CoA Carboxylase↗

PubMed1985

Effects of dietary fish protein, soybean protein and casein on cholesterol turnover in rats.

The effects of dietary fish, soybean protein and casein on cholesterol turnover were compared in rats. After the injection of [14C]cholesterol into the rats, the specific activities of radioactive cholesterol in feces were followed for 4 weeks. The cholesterol half-lives calculated from the decay curves of the specific activities were 14.7 and 14.6 days in rats fed fish protein and soybean protein, respectively. These were shorter than the half-life (17.4 days) in casein-fed controls. The fish and the soybean protein feedings significantly increased the fecal excretions of cholesterol and coprostanol, respectively, and lowered the plasma cholesterol level, as compared with casein feeding. In addition, both fish and soybean protein feedings also increased the excretion of bile acids. The stimulation of cholesterol metabolism and the increased excretions of cholesterol and its metabolites by feeding fish or soybean protein appear to play important roles in the hypocholesterolemic effects.

Animals↗

PubMed1985

Comparison of serum phospholipid fatty acids among fishing and farming Japanese populations and American inlanders.

Fatty acid compositions of phospholipids in serum were analyzed in three different populations in seaside fishing and mountain farming villages in Japan and in inland inhabitants of the United States of America. The percentage of omega-3 polyunsaturated fatty acids, i.e., eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) was significantly low in United States inlanders with a high coronary heart disease morbidity compared with both populations in Japan with low morbidity. The level of arachidonic acid (20:4) was the same among these three inhabitant population groups. However, omega-3 polyunsaturated fatty acid levels were significantly higher in the inhabitants of fishing villages with relatively low stroke morbidity than in those of farming villages with extremely high stroke morbidity in Japan.

Agriculture↗

PubMed1984

Effect of aging on changes in substrate and effector levels of rat-liver glycolytic and lipogenic enzymes during induction.

When 1-, 2- and 9-month-old rats adapted to a stock diet were fed a fat-free/high-sucrose diet, the changes in the substrate and effector levels of glycolytic and lipogenic enzymes in liver, and the effects of aging on the changes were investigated. By the sucrose diet feeding, the activities of phosphofructokinase, pyruvate kinase and fructokinase were increased, whereas hexokinase activity was markedly decreased. The fructose 1-phosphate levels were significantly increased in the liver, while conversely, the glucose 6-phosphate and fructose 6-phosphate levels were decreased. As a result of sucrose diet feeding, the changed enzyme activities would appear to be consistent with the metabolic pathway for fructose being predominant over that for glucose. Consequently, the concentrations of acetyl-CoA, citrate and malate were increased and would in turn appear to favour an increase in lipogenesis. The changes in the substrate and effector levels of lipogenic enzymes were reduced with aging, as were those in the enzyme activities. However, the changes in enzyme activities and metabolite levels of glycolysis were not much affected with aging.

Acetyl-CoA Carboxylase↗

PubMed1984

Changes of arachidonic acid and n-3 polyunsaturated fatty acids of phospholipid classes in liver, plasma and platelets during dietary fat manipulation.

When rats adapted to a fat-free diet were fed a corn oil diet, endogenous n-9 eicosatrienoic acid (the major polyunsaturated fatty acid) at the C-2 position of both phosphatidylcholine and phosphatidylethanolamine was quickly substituted by arachidonic acid in liver, plasma and platelets. Comparably, under a fish oil diet, the n-9 was quickly substituted by n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In both cases the n-9 almost disappeared in 6 days. On the other hand, when the dietary process was reversed, arachidonic acid in both the phospholipid classes (especially in phosphatidylcholine) decreased more slowly than the n-3 in the platelets and the liver mitochondria and microsomes. In platelets, even in linoleate-deficient rats, much arachidonic acid remained. However, arachidonic acid decreased similarly to the n-3 in the plasma. These results may reveal the physiological significance of arachidonic acid in membrane phospholipids, the replacement of arachidonic acid by the n-3 and the limitation of the replacement.

Animals↗