Carbohydrate responsive element-binding protein (ChREBP): a key regulator of glucose metabolism and fat storage.

Feeding a high carbohydrate diet induces transcription of more than 15 genes involved in the metabolic conversion of glucose to fat. A new transcription factor binding to a glucose response element of the pyruvate kinase and lipogenesis enzyme genes was discovered recently. This factor, termed carbohydrate responsive element-binding protein (ChREBP), is activated in response to high glucose and up-regulates these genes. Cyclic AMP and a high fat diet inhibit ChREBP and slow down glucose utilization. ChREBP is able to control transcription of lipogenic enzyme genes in response to nutritional and hormonal inputs, and may play an important role in disease states such as diabetes, obesity, and hypertension.

[1]  R. Troiano,et al.  Overweight prevalence among youth in the United States: Why so many different numbers? , 1999, International Journal of Obesity.

[2]  D. Granner,et al.  The genes of hepatic glucose metabolism. , 1990, The Journal of biological chemistry.

[3]  Ruihuan Chen,et al.  Transcriptional Glucose Signaling through The Glucose Response Element Is Mediated by the Pentose Phosphate Pathway (*) , 1996, The Journal of Biological Chemistry.

[4]  M. Nishimura,et al.  Glucose-stimulated synthesis of fructose 2,6-bisphosphate in rat liver. Dephosphorylation of fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase and activation by a sugar phosphate. , 1994, The Journal of biological chemistry.

[5]  J V Neel,et al.  The "thrifty genotype" in 1998. , 2009, Nutrition reviews.

[6]  J. Casazza,et al.  The content of pentose-cycle intermediates in liver in starved, fed ad libitum and meal-fed rats. , 1986, The Biochemical journal.

[7]  H. Shih,et al.  Carbohydrate Regulation of Hepatic Gene Expression , 1997, The Journal of Biological Chemistry.

[8]  H. Towle,et al.  Localization of the carbohydrate response element of the rat L-type pyruvate kinase gene. , 1991, The Journal of biological chemistry.

[9]  H. Towle,et al.  Carbohydrate regulation of the rat L-type pyruvate kinase gene requires two nuclear factors: LF-A1 and a member of the c-myc family. , 1993, The Journal of biological chemistry.

[10]  X. Hua,et al.  Sterol Resistance in CHO Cells Traced to Point Mutation in SREBP Cleavage–Activating Protein , 1996, Cell.

[11]  M. Vasseur-Cognet,et al.  Glucose Regulation of Gene Transcription* , 2000, The Journal of Biological Chemistry.

[12]  M. Díaz-Guerra,et al.  Cis-regulation of the L-type pyruvate kinase gene promoter by glucose, insulin and cyclic AMP. , 1992, Nucleic acids research.

[13]  A. Kahn,et al.  Respective roles of glucose, fructose, and insulin in the regulation of the liver-specific pyruvate kinase gene promoter. , 1994, The Journal of biological chemistry.

[14]  X. Hua,et al.  Sterol-Regulated Release of SREBP-2 from Cell Membranes Requires Two Sequential Cleavages, One Within a Transmembrane Segment , 1996, Cell.

[15]  S. Koo,et al.  Glucose regulation of mouse S(14) gene expression in hepatocytes. Involvement of a novel transcription factor complex. , 2000, Journal of Biological Chemistry.

[16]  K. Uyeda,et al.  Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Sakurai,et al.  A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  H. Yamashita,et al.  Mechanism for Fatty Acid “Sparing” Effect on Glucose-induced Transcription , 2002, The Journal of Biological Chemistry.

[19]  J. Hasegawa,et al.  A Novel Factor Binding to the Glucose Response Elements of Liver Pyruvate Kinase and Fatty Acid Synthase Genes* , 1999, The Journal of Biological Chemistry.

[20]  T. Tanaka,et al.  Characterization and purification of carbohydrate response element-binding protein of the rat L-type pyruvate kinase gene promoter. , 1999, Biochemical and biophysical research communications.

[21]  A. Goodridge Dietary regulation of gene expression: enzymes involved in carbohydrate and lipid metabolism. , 1987, Annual review of nutrition.

[22]  H. Shih,et al.  Regulation of the expression of lipogenic enzyme genes by carbohydrate. , 1997, Annual review of nutrition.

[23]  T. Osborne,et al.  Sterol Regulatory Element-binding Proteins (SREBPs): Key Regulators of Nutritional Homeostasis and Insulin Action* , 2000, The Journal of Biological Chemistry.

[24]  J. Girard,et al.  Induction of fatty-acid-synthase gene expression by glucose in primary culture of rat hepatocytes. Dependency upon glucokinase activity. , 1995, European journal of biochemistry.

[25]  J. Girard,et al.  Mechanisms by which carbohydrates regulate expression of genes for glycolytic and lipogenic enzymes. , 1997, Annual review of nutrition.

[26]  E. Duplus,et al.  Fatty Acid Regulation of Gene Transcription* , 2000, The Journal of Biological Chemistry.

[27]  H. Towle Metabolic Regulation of Gene Transcription in Mammals (*) , 1995, The Journal of Biological Chemistry.

[28]  J. Goldstein,et al.  The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor , 1997, Cell.

[29]  S. Vaulont,et al.  Exploration of a liver-specific, glucose/insulin-responsive promoter in transgenic mice. , 1993, The Journal of biological chemistry.

[30]  M. Nishimura,et al.  Purification and Characterization of a Novel Xylulose 5-Phosphate-activated Protein Phosphatase Catalyzing Dephosphorylation of Fructose-6-phosphate,2-kinase:Fructose-2,6-bisphosphatase (*) , 1995, The Journal of Biological Chemistry.

[31]  R. Roeder,et al.  Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. , 1983, Nucleic acids research.

[32]  M. Foretz,et al.  Induction of fatty acid synthase and S14 gene expression by glucose, xylitol and dihydroxyacetone in cultured rat hepatocytes is closely correlated with glucose 6-phosphate concentrations. , 1997, The Biochemical journal.