Artículos de revistas
Metabolic stress - Induced activation of FoxO1 triggers diabetic cardiomyopathy in mice
Fecha
2012Registro en:
Journal of Clinical Investigation, Volumen 122, Issue 3, 2018, Pages 1109-1118
00219738
15588238
10.1172/JCI60329
Autor
Battiprolu, Pavan K.
Hojayev, Berdymammet
Jiang, Nan
Wang, Zhao V.
Luo, Xiang
Iglewski, Myriam
Shelton, John M.
Gerard, Robert D.
Rothermel, Beverly A.
Gillette, Thomas G.
Lavandero González, Sergio
Hill, Joseph A.
Institución
Resumen
The leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cell