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Background:Bacterial endotoxin lipopolysaccharide(LPS)is a main initiator of sepsis, which,is responsible for inflammatory events and multiorgan dysfunction,could lead to myocardial depression that is a common feature of endotoxemia Adiponectin is an important adipocytokine Accumulating experimental evidence has indicated that adiponectin possesses anti-inflammatory,anti-atherogenic, anti-diabetic properties and plays an important role in its cardiovascular implications This study was designed to test the potent new-mechanism(s)that adiponectin may protect against LPS-induced cardiac d37sfunction Methods:LPS(4mg/kg)was injected into the abdomen in age-matched(5-6 month old)C57 and APO mice 6 hours priorto sacrifice Andmechanical properties ofisolated cardiacmyocytes aswell as analysis ofwestern blot,caspase-3 activation,ROS production,GSSG/GSH detection,TUNEL from cardiac tissues,inflammatory t'actors,pAMPK-mTOR-autophgic signals were examined AICAR((5-aminoimidazole-4-carboxamide-3-ribonucleoside,AMPK stimulator)were used to delineate whether the protective mechanism(s)of adiponectin in LPS challenge Results:LPS injection led to depressed PS,+dL/dt,and prolonged TR90 in C57mice,all ofwhich were exaggerated by adiponectin knockout LPS-induced caspase-3 activation,ROS generation,apoptosis,were significantly increased in APO mice compared with C57mice On the contrary,autophagy was significantly increased in C57 mice than that in APO ice as evidenced by increased expression of LC3II and decreased expression ofP62 LPS-induced contractile dysfuncfion was reversed by AICAR Conclusion:Our data suggests that adiponectin may protect against LPS-induced cardiac dysfunction by AMPK mediated autophagic signaling pathways.