Cardiac Peroxisome Proliferator-activated Receptor-β Activity is Up-regulated in the Absence of Muscle RING Finger-3, and Exaggerates High-fat Diet-induced Cardiomyopathy

Diabetic cardiomyopathy is characterized by structural and functional alterations leading to cardiac hypertrophy and heart failure. These changes are regulated in part by PPAR signaling and subsequent changes in fatty acid metabolism. We recently identified that mice lacking ubiquitin ligase Muscle RING Finger-3 (MuRF3-/-) have increased cardiac PPAR-β activity in vivo. We hypothesized that challenging MuRF3-/- mice with a high-fat diet, where lipids act as PPAR ligands, would enhance the severity of diabetic cardiomyopathy. MuRF3-/- mice and strain-matched controls were fed a high-fat diet. Serum insulin and glucose were measured every two weeks. Total cholesterol and serum triglycerides (TG) were measured at baseline and 26 weeks. Echocardiography was performed every three weeks. MuRF3-/- mice have less blood glucose after 26 weeks on high fat diet (HFD) as compared to strain-matched controls (168.8±6.2 vs. 240.2±15.5 mg/dL, P<0.05) and increased fasting insulin levels relative to controls (4.7±0.3 vs. ...