the critical role of astragalus polysaccharides for the improvement of ppraα-mediated lipotoxicity in diabetic cardiomyopathy黄芪多糖的关键作用的提高ppraα-mediated lipotoxicity在糖尿病心肌病.pdfVIP

The Critical Role of Astragalus Polysaccharides for the Improvement of PPRAa-Mediated Lipotoxicity in Diabetic Cardiomyopathy 1 1 1 3 1 1 2 Wei Chen , Yanping Xia , Xuelan Zhao , Hao Wang , Wenjie Chen , Maohua Yu , Yiming Li , 2 1 Hongying Ye *, Yu Zhang * 1 Department of Geriatrics, Hushan Hospital, Fudan University School of Medicine, Shanghai, China, 2 Department of Endocrinology, Huashan Hospital, Fudan University School of Medicine, Shanghai, China, 3 Core Center of Animal Facility, Fudan University School of Medicine, Shanghai, China Abstract Background: Obesity-related diabetes mellitus leads to increased myocardial uptake and oxidation of fatty acids, resulting in a form of cardiac dysfunction referred to as lipotoxic cardiomyopathy. We have shown previously that Astragalus polysaccharides (APS) administration was sufficient to improve the systemic metabolic disorder and cardiac dysfunction in diabetic models. Methodology/Principal Findings: To investigate the precise role of APS therapy in the pathogenesis of myocardial lipotoxity in diabetes, db/db diabetic mice and myosin heavy chain (MHC)- peroxisome proliferator-activated receptor (PPAR) a mice were characterized and administrated with or without APS with C57 wide- type mice as normal control. APS treatment strikingly improved the myocyte triacylglyceride accumulation and cardiac dysfunction in both db/db mice and MHC-PPARa mice, with the normalization of energy metabolic derangements in both db/db diabetic hearts and MHC- PPARa hearts. Consistently, the activation of PPARa target genes involved in myocardial fatty acid uptake and oxidation in both db/db diabetic hearts