Obesity-related disorders are associated with the development of ischemic heart 
disease. Adiponectin is a circulating adipose-derived cytokine that is 
downregulated in obese individuals and after myocardial infarction. Here, we 
examine the role of adiponectin in myocardial remodeling in response to acute 
injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in 
increased myocardial infarct size, myocardial apoptosis and tumor necrosis 
factor (TNF)-alpha expression compared with wild-type mice. Administration of 
adiponectin diminished infarct size, apoptosis and TNF-alpha production in both 
APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited 
apoptosis and TNF-alpha production. Dominant negative AMP-activated protein 
kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but 
had no effect on the suppressive effect of adiponectin on TNF-alpha production. 
Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin 
E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of 
adiponectin on TNF-alpha production and infarct size. These data suggest that 
adiponectin protects the heart from ischemia-reperfusion injury through both 
AMPK- and COX-2-dependent mechanisms.