Ami Aronheim
The B. Rappaport Faculty of Medicine, Israel
Posters & Accepted Abstracts: J Clin Exp Cardiolog
Obesity and type 2 diabetes (T2D) trigger a harmful stress-induced cardiac remodeling process known as cardiomyopathy. These diseases represent a serious and widespread health problem in the Western world, however, the underlying molecular basis is not clear. ATF3 is an "immediate early" transcription factor whose expression is highly and transiently induced in response to multiple stressors. All cellular stresses that play a role in T2D-induced cardiomyopathy, namely, metabolic stress, oxidative stress, ER stress and inflammation, are inducers of ATF3 transcription. Here we show that mice with cardiac-specific ATF3 deficiency (ATF3-cKO) exhibit severe cardiac fibrosis, higher levels of heart hypertrophic markers, increased inflammation and worse cardiac function, as compared to wild-type mice in response to a high-fat diet (HFD). These results demonstrate that ATF3 has a protective role, dampening HFD-induced cardiac remodeling. Remarkably, HFD-fed ATF3-cKO mice display increased hyperglycemia and poor glucose tolerance, despite higher blood insulin levels, as compared to HFD-fed wild-type mice. This is the first indication that heart tissue plays a role in regulating blood glucose levels, similar to skeletal muscle. Collectively, our results suggest that cardiac-specific ATF3 expression exerts both local and systemic effects related to T2D-induced cardiomyopathy.
Email: aronheim@tx.technion.ac.il
