TRB3 Gene Silencing Alleviates Diabetic Cardiomyopathy in

OBJECTIVE—Tribbles 3 (TRB3) is associated with insulin resis-tance, an important trigger in the development of diabetic cardio-myopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved. RESEARCH DESIGN AND METHODS—The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozo-tocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM. RESULTS—Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found tha