Adiponectin up-regulates the decrease of myocardial autophagic flux induced by β1-adrenergic receptor antibody partly dependent on AMPK

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β1 -adrenergic receptor autoantibody (β1 -AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β1 -AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up-regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β1 -AA by up-regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β1 -AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β1 -AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β1 -AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β1 -AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β1 -AA in cardiomyocytes. This study is the first time to confirm that β1 -AA could inhibit myocardial autophagic flux by down-regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β1 -AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β1 -AA-positive cardiac dysfunction.