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N Iritani

Publications and source records attributed to N Iritani.

At least 19 recordsLinked to original sources
PubMed1995

Diet differentially regulates glucokinase and L-type pyruvate kinase gene expression in rat liver.

The regulation of gene expression of glucokinase (GK) and L-type pyruvate kinase (L-PK) in rat liver was investigated and compared with the previously reported regulation of lipogenic enzymes. Experiments were conducted in which the time courses and responses to diet quantity of mRNA concentrations and enzyme activities after refeeding a carbohydrate/protein diet (CP) to food-deprived rats were measured. The effects of dietary nutrients on the gene expression were investigated in rats refed either the CP diet, a carbohydrate diet without protein (C), a protein diet without carbohydrate (P), or a carbohydrate/protein/corn oil diet (CPF). The effects of the CPF diet on the gene expression after insulin treatment to diabetic rats were also investigated. After refeeding the CP diet, GK mRNA concentration and enzyme activity reached maximum levels in 2 h and 16-24 h, respectively, whereas those of L-PK peaked in 16 h and 48 h, respectively, similar timecourse to lipogenic enzymes. Moreover, GK mRNA concentrations were maximal in rats fed 20% of the ad libitum diet intake, and L-PK mRNA concentrations, like lipogenic enzyme mRNA, were maximal in rats fed approximately 50% of ad libitum intake. GK mRNA concentrations were significantly increased in parallel with an increase in plasma insulin and glucose concentrations. GK and L-PK mRNA and enzyme levels in rats fed the C diet were comparably induced to the levels in those fed the CP diet. L-PK mRNA induction by the CP diet was significantly reduced by dietary polyunsaturated fatty acids (CPF diet), whereas the GK mRNA induction was not significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Polyunsaturated fatty acid-mediated suppression of insulin-dependent gene expression of lipogenic enzymes in rat liver.

The effects of dietary polyunsaturated fat on insulin-dependent gene expression of lipogenic enzymes and a possible mechanism for PUFA-mediated suppression of the gene expression have been investigated in rat livers. When diabetic rats were injected with insulin, the insulin dose-dependent induction of lipogenic enzyme mRNAs were markedly reduced with increasing dietary corn oil. On the other hand, the PUFA-mediated suppression of the mRNA concentrations was partially restored by treatment with pioglitazone, a candidate for increasing insulin receptor phosphorylation. Moreover, insulin binding to receptors of liver, receptor autophosphorylation, and kinase activity toward exogenous substrate were lower in the corn oil diet group than in the hydrogenated fat group. The PUFA-mediated suppression of insulin binding was somewhat restored by pioglitazone, and the suppression of insulin receptor phosphorylation was significantly restored. It is suggested that the PUFA-mediated suppression of insulin-dependent gene expression of lipogenic enzymes can be ascribed to a decrease in insulin receptor binding primarily and also to receptor phosphorylation. Thus, PUFA appears to suppress the lipogenic enzyme gene expression stimulated by insulin.

ATP Citrate (pro-S)-Lyase↗
PubMed1992

Effects of nutrients and hormones on gene expression of ATP citrate-lyase in rat liver.

Northern-blot analyses demonstrated a strong gene expression of ATp citrate-lyase in liver and adipose tissue of rat and a weak expression in brain, heart, small intestine and muscle. After refeeding a carbohydrate/protein diet to fasted rats, the transcriptional rate had already increased within 2 h, the mRNA concentration reached a maximal level of approximately 30-fold increased in 16 h, and the enzyme induction increased sixfold in 48 h. By feeding only carbohydrate without protein, the transcriptional rate was increased threefold, and the mRNA concentration and enzyme induction comparably, to the levels in the carbohydrate/protein diet. It appears that protein feeding is not necessary to induce ATP citrate-lyase. In diabetic rats fed on a glucose diet, the transcriptional rate, mRNA concentration and enzyme level were very low in comparison with the normal. By fructose feeding, however, the transcriptional rate was more greatly increased and the mRNA concentration increased comparably to the levels reached by insulin treatment, while the enzyme induction was not so increased. Thus, it is suggested that insulin is important in regulated translation in addition to transcription. However, triiodothyronine treatment did not have much effect on the gene expression. As a result of the present experiment, it is noted that ATP citrate-lyase-gene expression was greatly dependent on carbohydrate.

ATP Citrate (pro-S)-Lyase↗
PubMed1992

Regulation of hepatic lipogenic enzyme gene expression by diet quantity in rats fed a fat-free, high carbohydrate diet.

This investigation concerns the effects of the level of intake of a high carbohydrate diet on transcriptional rate, mRNA concentration and enzyme induction for lipogenic enzymes in rat liver. Six hours after refeeding fasted rats, the transcriptional rates in livers reached low maximum levels with small quantities of diet, but the mRNA concentrations continued to increase as diet intake increased. Greater diet intake primarily increased transcriptional rates and mRNA concentrations of lipogenic enzymes. After refeeding for 16 h, the mRNA concentrations were sigmoidly increased relative to the diet quantity and reached maximum levels of 20-, 110-, 22- and 16-fold above each fasted level for acetyl-CoA carboxylase, fatty acid synthase, malic enzyme and glucose-6-phosphate dehydrogenase, respectively. After 3 d of refeeding (in a steady state of lipogenic enzyme activities), however, the transcriptional rates, mRNA concentrations and activity inductions of all the enzymes were sigmoidly increased relative to diet quantity, but were not different among the enzymes. Consequently, fatty acid synthesis and triglyceride levels in the liver were not increased by feeding less than 70% of ad libitum intake but were greatly increased by feeding greater than 70% of ad libitum intake.

Acetyl-CoA Carboxylase↗
PubMed1992

Nutritional and hormonal regulation of mRNA levels of lipogenic enzymes in primary cultures of rat hepatocytes.

The effects of nutrients and hormones on the mRNA levels of acetyl-CoA carboxylase, fatty acid synthase, malic enzyme, and glucose 6-phosphate dehydrogenase were examined in primary cultures of rat hepatocytes during the process of induction. The addition of both glucose and insulin to the culture medium markedly enhanced the lipogenic enzyme mRNA induction due to either of them, in 16 h. Fructose or glycerol proved to be an effective substitute for glucose, suggesting that glycolytic metabolites were involved in the mRNA induction. It is remarkable that mRNA induction of acetyl-CoA carboxylase was the most sensitive to glucose and also to insulin among the lipogenic enzymes. Polyunsaturated fatty acids markedly reduced the mRNA induction of lipogenic enzymes. Dexamethasone enhanced all the lipogenic enzyme mRNA induction by insulin. On the other hand, triiodothyronine addition greatly increased the mRNA concentrations of lipogenic enzymes, but dexamethasone decreased rather than increased the mRNA induction by triiodothyronine. The effects of insulin on the induction of the lipogenic enzyme mRNAs were similar, but those of triiodothyronine were not. Triiodothyronine markedly enhanced malic enzyme mRNA induction by insulin with dexamethasone, and tended to enhance the induction of the acetyl-CoA carboxylase and fatty acid synthase mRNAs, but not that of glucose 6-phosphate dehydrogenase mRNA. It appeared that insulin and triiodothyronine synergistically enhanced lipogenic enzyme mRNA induction by glucose, but the mechanisms were different.

Acetyl-CoA Carboxylase↗
PubMed1992

Effects of aging on gene expression of acetyl-CoA carboxylase and fatty acid synthase in rat liver.

After refeeding a fat-free diet to fasted rats, the time courses of transcriptional rates, mRNA concentrations, and enzyme induction of hepatic acetyl-CoA carboxylase and fatty acid synthase were compared between 1.5- and 18-month-old rats. In the old rats, the levels were mostly 40-70% of those in the young animals. Moreover, the peaks of the levels tended to be delayed in the old animals. The transcriptional rates were increased within only 1 h after the refeeding in the young animals, but not until 6 h in the old. The mRNA concentrations reached maximum at 16 h in the young rats, but at 24 h in the old. In the old rats, the incorporation of [3H]leucine into the enzyme proteins was also decreased roughly in proportion to the enzyme induction. The mRNA concentrations in the liver polysomes were roughly proportional to the total mRNAs. Thus, the translational activities did not appear to be altered by aging. It is suggested that the age-dependent decreases of acetyl-CoA carboxylase and fatty acid synthase induction can be mainly ascribed to the transcriptional steps.

Acetyl-CoA Carboxylase↗
PubMed1992

Molecular mechanism of induction of key enzymes related to lipogenesis.

Key enzymes related to lipogenesis in the liver are induced by a high glucose diet or insulin and suppressed by starvation, diabetes, or glucagon. Most of these enzymes are also induced by dietary fructose, even in diabetic liver. This regulation occurs at the posttranscriptional level as well as at the transcriptional level. We studied extensively the molecular mechanism of induction of L-type pyruvate kinase (LPK). The transcription of the LPK gene in the liver was stimulated by insulin and inhibited by glucagon. This insulin action required ongoing protein synthesis and metabolism of glucose and was enhanced by glucocorticoid. On the other hand, the mechanism of induction of the LPK by dietary fructose depended on plasma insulin levels. Dietary fructose stimulated transcription of the LPK gene in normal rats, whereas it acted mainly at the posttranscriptional level in diabetic rats. These fructose effects were attributable to a common metabolite of fructose and glycerol. The induction of LPK mRNA by dietary glucose was impaired in the liver of Wistar fatty rats, a model of obese non-insulin-dependent diabetes mellitus, but fructose-induced accumulation of the mRNA was not. Studies on transgenic mice indicated that the 5'-flanking region up to -3 kb of the LPK gene contained all cis-acting elements necessary for tissue-specific expression of LPK and its stimulation by diets and insulin. Further analysis using a transient expression assay revealed the presence of three cis-acting elements necessary for expression of LPK in hepatocytes in the region up to -170 kb. However, these elements alone were not sufficient for dietary and hormonal regulation of this enzyme when analyzed in transgenic mice.

Animals↗
PubMed1991

Diurnal variations of lipogenic enzyme mRNA quantities in rat liver.

The diurnal variations in mRNA quantities of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, malic enzyme and glucose-6-phosphate dehydrogenase) in rat livers were detected. When the rats began feeding actively after lights out at 1900 h, the mRNA quantities were high from 0500 h to 0900 h in the morning. The variation in fatty acid synthase mRNA quantities was the most dramatic. However, no measurable variation in any enzyme levels including fatty acid synthase was detected. It may be because the half-lives of the enzymes are too long to be effected by the mRNAs which were high for several hours.

Acetyl-CoA Carboxylase↗
PubMed1990

Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver.

The effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver were investigated following cDNA cloning. When fasted rats were fed a carbohydrate/protein diet, the transcriptional rate was greatly increased even in 1 h. The transcriptional rate, mRNA concentration and enzyme induction reached maximum levels in 4 h, 8-16 h and 48 h, respectively. Although dietary carbohydrate increased each level more than protein did, both carbohydrate and protein were required to reach a high level. Corn oil feeding markedly decreased the transcriptional rate. In diabetic rats, the transcriptional rate, mRNA concentration and enzyme induction were very low in comparison with the normal. By treating the diabetic rats with insulin, however, the transcriptional rate was increased 5-fold in 1 h and 15-fold in 6 h, preceding a great increase in the mRNA and enzyme levels. On the other hand, fructose feeding or triiodothyronine treatment of diabetic rats abundantly increased the mRNA concentration and somewhat increased the transcriptional rate. Thus, it is suggested that insulin mainly stimulates the transcription of the fatty acid synthase gene, whereas triiodothyronine and fructose mainly increase the mRNA stability.

Animals↗
PubMed1990

Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase in rat liver.

The effects of nutrients and hormones on transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase in rat liver were investigated following a cDNA cloning. After refeeding a carbohydrate/protein diet to fasted rats, the transcriptional rate was increased 2.5-fold in only 1 h. The mRNA concentration reached a maximal level of 9-12-fold increase in 8-16 h, and the enzyme induction increased 10-fold in 48 h. By a carbohydrate diet without protein, the transcriptional rate, mRNA concentration and enzyme induction were similarly increased to the levels in the carbohydrate/protein diet. It appears that protein feeding is not necessary to induce acetyl-CoA carboxylase. Corn oil feeding decreased the transcriptional rate. In diabetic rats, the transcriptional rate, mRNA concentration and enzyme induction were very low in comparison with the normal. After insulin treatment, the transcriptional rate was increased 2-fold (the normal level) in 2 h in diabetic rats. By fructose feeding to diabetic rats, the transcriptional rate and mRNA concentration were increased similarly to the levels reached by insulin treatment, while the enzyme induction was increased by only 60%. Thus, it is suggested that insulin is importantly involved in the transcription and also translation of acetyl-CoA carboxylase. On the other hand, triiodothyronine treatment increased the mRNA and enzyme levels in diabetic and normal rats, and somewhat increased the transcriptional rate only in diabetic rats. Triiodothyronine appears to stabilize the mRNA besides having an insulin-like action in acetyl-CoA carboxylase transcription.

Acetyl-CoA Carboxylase↗
PubMed1990

Effects of ageing on transcriptional and post-transcriptional regulation of malic enzyme and glucose-6-phosphate dehydrogenase in rat liver.

We previously found an age-dependent impairment of induction of lipogenic enzymes in rat liver [Iritani et al. (1981) Biochim. Biophys. Acta 665, 636-639]. Further, we have found that after refeeding a fat-free diet to fasted rats, increases in transcriptional rate, mRNA concentration and enzyme induction of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were always lower in 18-month-old rats than in 1.5-month-old rats. In the young rats, the transcriptional rates reached the maximum level in 4 h and the mRNA reached maximum levels in 16 h. The peaks tended to delay in the older rats. The half-lives of the mRNAs were not significantly longer in the old than in the young animals. The incorporation of [3H]leucine into the enzyme proteins was also decreased roughly in proportion to the enzyme induction. The mRNA concentrations in the liver polysomes were roughly proportional to the total mRNA. Thus, no effects of ageing on mRNA stability or on the translational activity of the enzymes could be found. It is suggested that the age-dependent decreases of malic enzyme and glucose-6-phosphate dehydrogenase induction can be mainly ascribed to the transcriptional steps. Moreover, the transcriptional rate, mRNA concentration and induction of malic enzyme were increased by triiodothyronine treatment at a similar rate in both the young and old rats, but the absolute increments were lower in the old animals. The triiodothyronine response to malic enzyme induction also appeared to be primarily decreased at the transcription level.

Aging↗
PubMed1989

Effects of nutrients and insulin on transcriptional and post-transcriptional regulation of glucose-6-phosphate dehydrogenase synthesis in rat liver.

The transcriptional and post-transcriptional regulation of glucose-6-phosphate dehydrogenase induction of rat liver was investigated using a cDNA cloned in our laboratory. By feeding a carbohydrate/protein diet to fasted rats, the mRNA concentration and enzyme induction of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) reached maximal levels about 10-fold those in the fasted rats at 16 h and 72 h, respectively, whereas the transcriptional rate was increased about 3-fold in 6 h. In the protein fed (without carbohydrate) group, both the mRNA concentration and enzyme induction were increased to about 60% of the levels in the carbohydrate/protein fed group and in the group fed on a carbohydrate diet (without protein) to 30-40%. Further, dietary fat significantly reduced the transcriptional rate, mRNA concentration and enzyme induction to less than half, suggesting that dietary fat primarily reduced transcription. Thus, dietary nutrients appear to be involved in the steps preceding the translation. On the other hand, in diabetic rats, the transcriptional rate was significantly decreased as compared to the normal level and restored by insulin-treatment in 4 h. The mRNA concentration was very low in diabetic rats, and was restored to the normal level by insulin treatment in 8 h, and was half restored by fructose feeding. However, the enzyme induction of glucose-6-phosphate dehydrogenase was scarcely restored by fructose, unless accompanied by insulin treatment. Thus, it is suggested that insulin is involved in translation as well as in transcription. Further, the insulin-dependent increase of glucose-6-phosphate dehydrogenase mRNA was blocked by cycloheximide, suggesting that synthesis of a peptide is required.

Animals↗
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↗