TRB3 gene silencing ameliorated metabolic disturbance, insulin resistance, myocardial hypertrophy, lipids accumulation, inflammation, and fibrosis, improving cardiac function in a diabetic rat model.
Does TRB3 gene silencing alleviate diabetic cardiomyopathy in a type 2 diabetic rat model?
TRB3 gene silencing exerts a protective effect against diabetic cardiomyopathy in a rat model by improving selective insulin resistance, suggesting a potential therapeutic target.
OBJECTIVE: Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (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 streptozotocin. 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 that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased. CONCLUSIONS: TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM.
Ti et al. (Wed,) conducted a other in Diabetic cardiomyopathy. TRB3 gene silencing was evaluated on Pathophysiologic features of DCM including cardiac function, insulin resistance, and myocardial remodeling. TRB3 gene silencing ameliorated metabolic disturbance, insulin resistance, myocardial hypertrophy, lipids accumulation, inflammation, and fibrosis, improving cardiac function in a diabetic rat model.