Nesfatin-1 protects against diabetic cardiomyopathy in the streptozotocin-induced diabetic mouse model via the p38-MAPK pathway

Abstract

ABSTRACT Nesfatin-1 is a novel anorexigenic peptide that possesses antihyperglycemic and cardiovascular effects. We hypothesized that nesfatin-1 has a beneficial protective effect against diabetic cardiomyopathy (DC). We investigated the therapeutic effect of nesfatin-1 on diabetes-associated cardiac dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. We found that the cardiac nesfatin-1 level was lower in diabetic mice than in normal mice. Nesfatin-1 treatment (180 mg/kg/day for two weeks) improved insulin sensitivity and mitigated diabetic dyslipidemia. Nesfatin-1 ameliorated the diabetes-related myocardial hypertrophy and heart dysfunction, as revealed by the reduced hypertrophy index, heart rate, mean arterial pressure (MAP), creatine kinase (CK)-MB, and aspartate aminotransferase (AST) levels. Nesfatin-1 exerted antioxidant and anti-inflammatory activity in diabetic mice, as shown by decreased reactive oxygen species (ROS), oxidative lipid product malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH), decreased cardiac and plasma interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) levels. Mechanistically, we found that nesfatin-1 inhibited the cardiac p38-MAPK pathway activation and subsequent glucagon-like peptide-1 (GLP-1) level. Collectively, our data shows nesfatin-1 exerted protective effects against diabetic cardiomyopathy. Our study suggests that nesfatin-1 therapy has therapeutic implications against diabetic cardiomyopathy.