Reduced Cardioprotective Action of Adiponectin in High-Fat Diet–Induced Type II Diabetic Mice and Its Underlying Mechanisms

• DOI: 10.1089/ars.2010.3722
• Publication Date: 2010-11-21T15:31:05Z
• 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
• Keywords: Cardioprotection; AMP-Activated Protein Kinase

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