title: Astragalus polysaccharides repress myocardial lipotoxicity in a PPARalpha-dependent manner in vitro and in vivo in mice.
abstract: BACKGROUND
  The role of peroxisome proliferator-activated receptor alpha (PPARα) in the development of myocardial lipotoxicity is widely observed in diabetic disorders. Thus, we investigated if treatment of Astragalus polysaccharides modulates lipotoxic cardiomyopathy both in vivo and in vitro through PPARα mechanisms.
  
  
  RESULTS
  The effects of Astragalus polysaccharides (APS) on PPARα target gene expression and protein levels were tested in vitro and in vivo, including in mice with PPARα cardiac-restricted overexpression [myosin heavy chain (MHC)-PPARα] and in H9c2 embryonic rat cardiomyocytes with or without PPARα agonist. Echocardiographic studies, analyses of myocardial triglyceride and cardiac fuel utilization analyses were also performed in MHC-PPARα mice. Treatment with APS prevented myocardial triglyceride accumulation and cardiac dysfunction in the MHC-PPARα mice, with the normalization of energy metabolic derangements in hearts including reduced free fatty acids utilization and increased glucose uptake. Consistently, both in the MHC-PPARα hearts and H9c2 cardiomyocytes with PPARα agonist, the activation of PPARα gene regulatory pathway involved in FFA-oxidation was down-regulated by APS treatment, while the suppression of PPARα target genes involved in glucose uptake and oxidation was normalized by APS administration.
  
  
  CONCLUSIONS
  Therapy with APS could prevent the development of lipotoxic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARα-mediated regulatory pathways.
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: chenwei_0424@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Core Center of Clinical Skills Training, Fudan University school of Medicine, Shanghai 200032, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xuelan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: billycai56@yahoo.com.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Ye
mesh_terms: D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry*; D011134:Polysaccharides / Q000378:metabolism / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; D018995:Myosin Heavy Chains; D011345:Fenofibrate
keywords: Cardiomyocytes; Cardiomyopathy; H9c2; Lipid metabolism; Lipotoxity; PPARα