title: Therapy with Astragalus polysaccharides rescues lipotoxic cardiomyopathy in MHC-PPARα mice.
abstract: Obesity-related diabetes mellitus leads to lipotoxic cardiomyopathy resulting in a form of cardiac dysfunction. Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR) α showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart. To define the role of Astragalus Polysaccharides (APS) treatment for PPARα-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy, myosin heavy chain [MHC]-PPARα mice with high-fat diet were administrated with APS or vehicle for 16 weeks. The APS treatment prevented myocardial long-chain triglyceride accumulation, ultrastructure abnormality in cardiac myocytes and cardiac dysfunction in the MHC-PPARα mice, which was associated with reduced free fatty acids (FFA) utilization and increased glucose uptake and oxidation in hearts by APS treatment. Consistent with the metabolic changes, activation of PPARα gene regulatory pathway involved in FFA-oxidation in the MHC-PPARα heart was down-regulated by APS treatment, while suppression of PPARα target genes involved in glucose uptake and oxidation in the MHC-PPARα hearts was normalized by APS administration. We conclude that therapy with APS might lead to the inhibition of PPARα-mediate lipotoxicity in the pathogenesis of diabetic cardiomyopathy.
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University School of Medicine, Shanghai, 200040, China. chenwei_0424@163.com
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Chen
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xia
authors.forename: Xuelan
authors.initials: X
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Maohua
authors.initials: M
authors.lastname: Yu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Hongying
authors.initials: H
authors.lastname: Ye
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D011134:Polysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047493:PPAR alpha; D011134:Polysaccharides; D018995:Myosin Heavy Chains