Dietary response of various key enzymes related to glucose metabolism in normal and diabetic rat liver

Takeda, Yoshiro; Inoue, Hideo; Honjo, K.; Tanioka, Hiroaki; Daikuhara, Yasushi

doi:10.1016/0304-4165(67)90066-9

Cited by 71 publications

(12 citation statements)

References 42 publications

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“…[Also compatible with this hypothesis are previous findings that in diabetic animals the lowered hepatic activities of such enzymes as pyruvate kinase (27), ATP-citrate lyase (27), acetylCoA carboxylase (27) and A9-desaturase (stearic --oleic) (30) are increased toward normal or above by the feeding of glycerol. Glycerol, like fructose, enters the glycolytic pathway at the triose phosphate step.]…”

Section: Discussionsupporting

confidence: 53%

“…By this active pathway, fructose bypasses the first two slow steps in glycolysis, catalyzed by glucokinase and phosphofructokinase; in fact, fructose feeding results in 40-70% higher levels of pyruvate, acetyl-CoA, and malate in liver than does glucose feeding (26). These data have been invoked to explain the greater synthesis of fatty acids from glucose or fructose by liver slices from animals fed fructose compared to those fed glucose (26 (27) ]. This hypothesis would explain the higher concentration of synthetase in normal animals fed fructose rather than glucose.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Mammalian Fatty-Acid Synthetase. The Roles of Carbohydrate and Insulin

Volpe

Vagelos

1974

Proc. Natl. Acad. Sci. U.S.A.

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The regulation of fatty-acid synthetase has been studied in liver, adipose tissue, and brain of diabetic and normal rats in relation to insulin administration and glucose or fructose feeding. The data indicate that: (1) insulin is not necessary for regulation of synthetase activity in liver but may be necessary in adipose tissue; (2) synthetase of liver can be regulated by carbohydrate, which can enter the glycolytic scheme in the absence of insulin (e.g., fructose), suggesting the possibility that regulation of synthetase may depend on the concentration of certain intermediates of the glycolytic pathway or beyond; (3) fructose feeding affects the synthetase by causing an increase in the rate of synthesis of fatty-acid synthetase; and (4) unlike fatty-acid synthetase of liver and adipose tissue, the enzyme of brain is unaffected by the diabetic state or by glucose or fructose feeding.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Regulation of Mammalian Fatty-Acid Synthetase. The Roles of Carbohydrate and Insulin

Volpe

Vagelos

1974

Proc. Natl. Acad. Sci. U.S.A.

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“…This explanation, however, is not very likely. It is generally accepted that the capacity for NADPH generation is not limiting lipogenesis since the activities of the enzymes responsible for NADPH production are at least one order of magnitude higher than those of the enzymes involved in fatty acid synthesis per se irrespective of nutritional or hormonal state (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Effects of ethanol feeding on hepatic lipid synthesis

Tijburg

Maquedano

Bijleveld

et al. 1988

Archives of Biochemistry and Biophysics

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Rats were fed a high-fat, liquid diet containing either 36% of total calories as ethanol or an isocaloric amount of sucrose, for a period up to 35 days. At different time intervals we measured the effects of ethanol administration on the activities of a number of key enzymes involved in hepatic lipid synthesis. At the start of the experimental period the activities of acetyl-CoA carboxylase and fatty acid synthase, measured in liver homogenates, increased in the control as well as in the ethanol-fed group. After 35 days these enzyme activities were still elevated but there were no significant differences between the two groups. In hepatocytes isolated from controls as well as from ethanol-fed rats, short-term incubations with ethanol induced an increase in the rate of fatty acid synthesis and in the activities of acetyl-CoA carboxylase and fatty acid synthase. However, no alterations in the regulation of these enzymes by short-term modulators of lipogenesis were apparent in hepatocytes isolated from alcohol-treated animals. The results do not indicate a major role for the enzymes of de ncruo fatty acid synthesis in the development of the alcoholic fatty liver. The amount of liver triacylglycerols increased in ethanol-fed rats during the entire treatment period, whereas the hepatic levels of phosphatidylcholine and phosphatidylethanolamine were not affected by ethanol ingestion. Ethanol administration for less than 2 weeks increased the activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase, and microsomal phosphocholine cytidylyltransferase, whereas the cytosolic activity of phosphocholine cytidylyltransferase was slightly decreased. Upon prolonged ethanol administration the activities of these enzymes were slowly restored to control values after 35 days, suggesting development of some kind of adaptation. It is interesting that, although the activities of phosphatidate phosphohydrolase and diacylglycerol acyltransferase were restored to the levels found in the control rats, this effect was not accompanied by a stabilization or decrease of the concentration of hepatic triacylglycerols. 0 1988 Academic press, inc.

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“…The high K m hexokinase, glucokinase, supports the rapid uptake and metabolism of carbohydrate in hepatocytes. However, the regulation of glucokinase is independent of glucose and is directly exerted by insulin (37,38). Dominant negative Mlx did not interfere with the insulin induction of glucokinase mRNA levels (Fig.…”

Section: Dominant Negative MLX Does Not Affect Induction Of Genes By mentioning

confidence: 99%

Direct Role of ChREBP·Mlx in Regulating Hepatic Glucose-responsive Genes

Tsatsos

Towle

2005

Journal of Biological Chemistry

165

141

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Enzymes required for de novo lipogenesis are induced in mammalian liver after a meal high in carbohydrates. In addition to insulin, increased glucose metabolism initiates an intracellular signaling pathway that transcriptionally regulates genes encoding lipogenic enzymes. A cis-acting sequence, the carbohydrate response element (ChoRE), has been found in the promoter region of several of these genes. ChREBP (carbohydrate response element-binding protein) was recently identified as a candidate transcription factor in the glucose-signaling pathway. We reported that ChREBP requires the heterodimeric partner Max-like factor X (Mlx) to bind to ChoRE sequences. In this study we provide further evidence to support a direct role of Mlx in glucose signaling in the liver. We constructed two different dominant negative forms of Mlx that could dimerize with ChREBP but block its binding to DNA. When introduced into hepatocytes, both dominant negative forms of Mlx inhibited the glucose response of a transfected ChoRE-containing promoter. The glucose response was rescued by adding exogenous wild type Mlx or ChREBP, but not MondoA, a paralog of ChREBP that can also form a heterodimer with Mlx. Furthermore, dominant negative Mlx blocked the induction of glucose-responsive genes from their natural chromosomal context under high glucose conditions. In contrast, genes induced by the insulin and thyroid hormone-signaling pathways were unaffected by dominant negative Mlx. Mlx was present in the glucoseresponsive complex of liver nuclear extract from which ChREBP was purified. In conclusion, Mlx is an obligatory partner of ChREBP in regulating lipogenic enzyme genes in liver.

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Dietary response of various key enzymes related to glucose metabolism in normal and diabetic rat liver

Cited by 71 publications

References 42 publications

Regulation of Mammalian Fatty-Acid Synthetase. The Roles of Carbohydrate and Insulin

Regulation of Mammalian Fatty-Acid Synthetase. The Roles of Carbohydrate and Insulin

Effects of ethanol feeding on hepatic lipid synthesis

Direct Role of ChREBP·Mlx in Regulating Hepatic Glucose-responsive Genes

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