Permissive role of AMPK and autophagy in adiponectin deficiency-accentuated myocardial injury and inflammation in endotoxemia.

摘要: Abstract Background Adiponectin (APN), an adipose-derived adipokine, alleviates lipopolysaccharide (LPS)-induced injury in multiple organs including hearts although the underlying mechanism endotoxemia remains elusive. This study was designed to examine role of adiponectin LPS-induced cardiac anomalies and inflammation as well with a focus on autophagy — conserved machinery for bulk degradation intracellular components. Methods results Wild-type (WT) APN −/− mice were challenged LPS (4 mg/kg) or saline 6 h. Echocardiography, cardiomyocyte contractile Ca 2 + properties evaluated. Markers autophagy, apoptosis LC3B, p62, Beclin1, AMPK, mTOR, ULK, Caspase 3, Bcl-2, Bax, TLR4, TRAF6, MyD88, IL-1B, TNFα, HMGB1, JNK IκB examined using Western blot RT-PCR. Our showed that challenge reduced fractional shortening, compromised capacity, handling properties, inflammation, which accentuated by ablation. ablation unmasked remodeling (left ventricular end systolic diameter) prolongation cell shortening. The detrimental effects associated dampened response through AMPK-mTOR-ULK1-dependent mechanism. In vivo administration AMPK activator AICAR inducer rapamycin effectively attenuated obliterated deficiency-accentuated responses without affecting TRAF6 MyD88. Conclusions findings suggest may play permissive deficiency-exacerbated dysfunction, under possibly at post-TLR4 receptor level.