title: The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism.
abstract: Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP) is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase), fructolysis (Glut5, ketohexokinase), and lipogenesis (acetyl CoA carboxylase, fatty acid synthase). ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, becauseChrebp-/-mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.
authors.affiliation: Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. kiizuka@gifu-u.ac.jp.|Gifu University Hospital Center for Nutritional Support and Infection Control, Gifu 501-1194, Japan. kiizuka@gifu-u.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Iizuka
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D005631:Fructokinases / Q000235:genetics; D005632:Fructose / Q000009:adverse effects / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D051296:Glucose Transporter Type 5 / Q000235:genetics; D006019:Glycolysis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000209:etiology / Q000517:prevention & control; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051296:Glucose Transporter Type 5; C116385:MLXIPL protein, human; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D005632:Fructose; D005631:Fructokinases; C021475:ketohexokinase
keywords: ChREBP; Glut5/SLC2A5; carbohydrate response element binding protein; fructolysis; fructose; glycolysis; ketohexokinase