title: Overexpression of c-myc in the liver prevents obesity and insulin resistance.
abstract: Alterations in hepatic glucose metabolism play a key role in the development of the hyperglycemia observed in type 2 diabetes. Because the transcription factor c-Myc induces hepatic glucose uptake and utilization and blocks gluconeogenesis, we examined whether hepatic overexpression of c-myc counteracts the insulin resistance induced by a high-fat diet. After 3 months on this diet, control mice became obese, hyperglycemic, and hyperinsulinemic, indicating that they had developed insulin resistance. In contrast, transgenic mice remained lean and showed improved glucose disposal and normal levels of blood glucose and insulin, indicating that they had developed neither obesity nor insulin resistance. These findings were concomitant with normalization of hepatic glucokinase and pyruvate kinase gene expression and enzyme activity, which led to normalization of intrahepatic glucose-6-phosphate and glycogen content. In the liver of control mice fed a high-fat diet, the expression of genes encoding proteins that control energy metabolism, such as sterol receptor element binding protein 1-c, peroxisome proliferator activated receptor alpha, and uncoupling protein-2, was altered. In contrast, in the liver of transgenic mice fed a high-fat diet, the expression of these genes was normal. These results suggest that c-myc overexpression counteracted the obesity and insulin resistance induced by a high-fat diet by modulating the expression of genes that regulate hepatic metabolism.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, and Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, E-08193-Bellaterra, Spain.
authors.forename: Efren
authors.initials: E
authors.lastname: Riu
authors.forename: Tura
authors.initials: T
authors.lastname: Ferre
authors.forename: Antonio
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Alex
authors.initials: A
authors.lastname: Mas
authors.forename: Sylvie
authors.initials: S
authors.lastname: Franckhauser
authors.forename: Pedro
authors.initials: P
authors.lastname: Otaegui
authors.forename: Fatima
authors.initials: F
authors.lastname: Bosch
mesh_terms: D000818:Animals; D004032:Diet; D015536:Down-Regulation; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D006019:Glycolysis; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger