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.

Graphic abstract

KEYWORDS:

• Nesfatin-1
• diabetic cardiomyopathy (DC)
• streptozotocin-induced cardiac damages
• p38 MAPK
• inflammation
• oxidative stress

Acknowledgements

This study is funded by the “Youth Science Foundation of National Natural Science of China (NO. 81800323)” and the “Natural Science Foundation of Heilongjiang province (No. H2018032)”.

Ethical statements

This study conformed to the ethical guidelines of the Youth Science Foundation of National Natural Science of China.

Consent to publication

All the authors have read and approved the final submission of this study.

data-availability

Data of this study are available upon reasonable request to the corresponding authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author Contribution

Zhanwei Fan, Jianjiang Dong, and Xian Liu contributed to the study design. Zhanwei Fan, Jianjiang Dong, and Yindong Mu contributed to the experimental conduction and data collection. All authors critically reviewed the manuscript and approved the final draft.

Additional information

Funding

This work was supported by the Youth Science Foundation of National Natural Science of China [NO. 81800323]; Natural Science Foundation of Heilongjiang province [No. H2018032]; Youth Science Foundation of National Natural Science of China [NO. 81800323]; Natural Science Foundation of Heilongjiang province [No. H2018032]; Youth Science Foundation of National Natural Science of China [NO. 81800323]; Natural Science Foundation of Heilongjiang province [No. H2018032]; Youth Science Foundation of National Natural Science of China [NO. 81800323]; Natural Science Foundation of Heilongjiang province [No. H2018032].