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

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.

Oxymatrine and insulin resistance: Focusing on mechanistic intricacies involve in diabetes associated cardiomyopathy via SIRT1/AMPK and TGF‐β signaling pathway

“…[ 27 ] A study of Fan et al showed that treatment of streptozotocin and high fat diet (STZ‐HFD)‐induced diabetic rats with nesfatin‐1 attenuate cardiomyopathy by downregulating the p38 MAPK signaling pathway and associated cardiac apoptosis, fibrosis, inflammation, and oxidative stress. [ 28 ] A similar effect was observed in STZ‐induced diabetic mice where treatment with ivabradine exhibited cardioprotective effect by downregulating cardio‐specific p38 MAPK/JNK signaling and mediated inflammation, apoptosis, and oxidative stress. [ 29 ]…”

Progress in the treatment of diabetic cardiomyopathy, a systematic review

“…It is demonstrated that nicorandil, which activates the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (PKB) pathway, reduces cardiomyocyte apoptosis and improves the symptoms of cardiac insufficiency in DM rats 84 . Moreover, studies have shown that Nesfatin‐1 improves insulin sensitivity in STZ‐induced DM model rats through the p38‐MAPK pathway, reducing inflammation and ameliorating cardiac dysfunction 85 …”

“…84 Moreover, studies have shown that Nesfatin-1 improves insulin sensitivity in STZ-induced DM model rats through the p38-MAPK pathway, reducing inflammation and ameliorating cardiac dysfunction. 85 In recent years, extensive research has shown that certain herbal extracts have potential therapeutic effects on DCM. [86][87][88][89][90][91] For instance, Schisandrin B has been found to alleviate DCM by targeting MyD88 and inhibiting MyD88-dependent inflammation.…”

“… 84 Moreover, studies have shown that Nesfatin‐1 improves insulin sensitivity in STZ‐induced DM model rats through the p38‐MAPK pathway, reducing inflammation and ameliorating cardiac dysfunction. 85 …”

The Role of Adipokines in Inflammatory Mechanisms of Obesity

“…It has been found that nesfatin increases insulin sensitivity and has anti-inflammatory as well as cardioprotective effects. Thus, studies have shown that nesfatin inhibits MAPK signaling pathways, including p38 MAPK/c-Jun and IKK/NF-κB, and also reduces the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α [ 120 , 121 , 122 ]. In addition, it has been found that nesfatin affects indicators of oxidative stress, namely, it suppresses the increased production of ROS, and also increases the activity of superoxide dismutase [ 122 ].…”