Overexpression of c-myc in the liver prevents obesity and insulin resistance

被引:36
作者
Riu, E
Ferre, T
Hidalgo, A
Mas, A
Franckhauser, S
Otaegui, P
Bosch, F [1 ]
机构
[1] Univ Autonoma Barcelona, Sch Vet Med, Dept Biochem & Mol Biol, E-08193 Bellaterra, Spain
[2] Univ Autonoma Barcelona, Ctr Anim Biotechnol & Gene Therapy, E-08193 Bellaterra, Spain
关键词
transgenic mice; type; 2; diabetes; glucose metabolism;
D O I
10.1096/fj.02-1163fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 a, 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.
引用
收藏
页码:1715 / +
页数:20
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