| First Author | Chen W | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e45541 |
| PubMed ID | 23049681 | Mgi Jnum | J:191956 |
| Mgi Id | MGI:5463690 | Doi | 10.1371/journal.pone.0045541 |
| Citation | Chen W, et al. (2012) The critical role of Astragalus polysaccharides for the improvement of PPRAalpha-mediated lipotoxicity in diabetic cardiomyopathy. PLoS One 7(10):e45541 |
| abstractText | 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) alpha 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-PPARalpha mice, with the normalization of energy metabolic derangements in both db/db diabetic hearts and MHC-PPARalpha hearts. Consistently, the activation of PPARalpha target genes involved in myocardial fatty acid uptake and oxidation in both db/db diabetic hearts and MHC-PPARalpha hearts was reciprocally repressed by APS administration, while PPARalpha-mediated suppression of genes involved in glucose utilization of both diabetic hearts and MHC-PPARalpha hearts was reversed by treatment with APS. CONCLUSIONS: We conclude that APS therapy could prevent the development of diabetic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARalpha-mediated regulatory pathways. |
