Duodenal‐jejunal bypass surgery activates eNOS and enhances antioxidant system by activating AMPK pathway to improve heart oxidative stress in diabetic cardiomyopathy rats

Abstract

BackgroundDiabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal‐jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats.MethodsHigh‐fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro.ResultsDJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system‐related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system‐related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors.ConclusionsDJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway—and not solely by improving blood glucose—to improve oxidative stress in the heart of diabetic cardiomyopathy rats.

MARK4 aggravates cardiac dysfunction in mice with STZ-induced diabetic cardiomyopathy by regulating ACSL4-mediated myocardial lipid metabolism

“…The DCM model induced by low-dose STZ injection combined with high-fat diet has certain differences from other diabetic models. Although myocardial injury, myocardial apoptosis, increased oxidative stress, mitochondrial dysfunction, and impaired lipid metabolism in the DCM model have no significant differences from other diabetic models 38 – 47 . However, whether MARK4 intervention can also reduce myocardial apoptosis and myocardial oxidative stress, alleviate mitochondrial dysfunction and promote myocardial lipid metabolism in other diabetes models, which needs further research in the future.…”