Facilitated Ca 2+ homeostasis and attenuated myocardial autophagy contribute to alleviation of diabetic cardiomyopathy after bariatric surgery

Bariatric surgery has been reported to relieve diabetic cardiomyopathy (DCM) effectively. However, the mechanisms remain largely unknown. To determine the effects of bariatric surgery on DCM via modulation of myocardial Ca2+ homeostasis and autophagy, sleeve gastrectomy (SG), duodenal-jejunal bypass (DJB) and SHAM surgeries were performed in diabetic rats induced by high fat diet and low dose of streptozotocin. Cardiac remodeling was assessed by series of morphometric and histological analyses. Transthoracic echocardiography and hemodynamic measurement were performed to determine cardiac function. The Ca2+ homeostasis was evaluated by measuring Ca2+ transients with Fura-2/AM in isolated ventricular myocytes, along with detecting abundance of Ca2+ regulatory proteins in myocardium. The myocardial autophagic flux was determined by expression of autophagy-related proteins in the absence and presence of chloroquine (CQ). Both SG and DJB surgery alleviated diabetic cardiomyopathy morphologically and functionally. Ca2+ transients exhibited significantly higher amplitude and faster decay after SG and DJB, which could be partially explained by increased expression of ryanodine receptor 2 (RyR2), sarco/endoplasmic reticulum Ca2+-2ATPase (SERCA2a), FKBP12.6, and hyperphosphorylation of phospholamban. In addition, lower level of light chain 3 B (LC3B)-II and higher level of p62 were detected after both SG and DJB, which was not reversed by CQ treatment and associated with activated mTOR and attenuated AMP-activated protein kinase (AMPK) signaling pathway. Collectively, these results provided evidence that bariatric surgery could alleviate DCM effectively, which may result, at least in part, from facilitated Ca2+ homeostasis and attenuated autophagy, suggesting a potential choice for treatment of DCM when properly implemented.