Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms.

Authors

• Wei Yi
• Yang Sun
• Erhe Gao
• Xufeng Wei
• Wayne Bond Lau
• Qijun Zheng
• Yajing Wang
• Yuexing Yuan
• Xiaoliang Wang
• Ling Tao
• Rong Li
• Walter Koch
• Xin-Liang Ma

Publication/Presentation Date

10-1-2011

Abstract

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent seen in ND mice (i.e., infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP-activated protein kinase (AMPK)-dependent metabolic regulation and AMPK-independent antioxidative/antinitrative pathways. Compared to ND, HD mice manifested significantly blunted gAPN-induced AMPK activation, basally and after MI/R (p< 0.05). Although both low- and high-dose gAPN equally attenuated MI/R-induced oxidative stress (i.e., NADPH oxidase expression and superoxide production) and nitrative stress (i.e., inducible nitric oxide synthase expression, nitric oxide production, and peroxynitrite formation) in ND mice, only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent APN cardioprotection, suggesting an unreported diabetic heart APN resistance.

Volume

15

Issue

7

First Page

1779

Last Page

1788

ISSN

1557-7716

Published In/Presented At

Yi, W., Sun, Y., Gao, E., Wei, X., Lau, W. B., Zheng, Q., Wang, Y., Yuan, Y., Wang, X., Tao, L., Li, R., Koch, W., & Ma, X. L. (2011). Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. Antioxidants & redox signaling, 15(7), 1779–1788. https://doi.org/10.1089/ars.2010.3722

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

21091073

Department(s)

Administration and Leadership

Document Type

Article