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dc.contributor.authorNzirorera, Carine
dc.date.accessioned2017-08-09T18:33:57Z
dc.date.available2017-08-09T18:33:57Z
dc.identifier.urihttp://hdl.handle.net/10222/73098
dc.description.abstractThe metabolic changes to adipose tissue during obesity can induce cardiac insulin resistance. During obesity and diabetes, cardiac metabolic flexibility is reduced, which may lead to impaired ATP production, elevated reactive oxygen species production, mitochondrial dysfunction and apoptosis. The adipokine, autotaxin (ATX), which generates bioactive lipids called lysophosphatidic acids (LPA), has been linked to obesity-induced insulin resistance in both mouse models and humans. This study is the first to examine the role of ATX/LPA in obesity-induced cardiac insulin resistance, cardiac dysfunction and in palmitate-induced lipotoxicity. Pre-incubation with LPA reduced the magnitude of insulin stimulation of AKT compared to baseline. In the presence of palmitate, LPA exacerbated cardiac insulin resistance in H9C2 cells and neonatal rat cardiomyocytes. Lastly, a reduction in ATX/LPA levels protected against obesity-induced cardiac insulin resistance and cardiac dysfunction. Collectively, these results suggest increasing levels of ATX/LPA aide in the progression of cardiomyopathy during obesity and insulin resistance/diabetes.en_US
dc.language.isoenen_US
dc.subjectObesityen_US
dc.subjectLPAen_US
dc.subjectPalmitateen_US
dc.subjectCardiomyopathyen_US
dc.subjectDiabetesen_US
dc.subjectSarcomere Shorteningen_US
dc.titleTHE ROLE OF LYSOPHOSPHATIDIC ACID AND AUTOTAXIN IN OBESITY-INDUCED CARDIAC INSULIN RESISTANCEen_US
dc.date.defence2017-08-04
dc.contributor.departmentDepartment of Biochemistry & Molecular Biologyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinern/aen_US
dc.contributor.graduate-coordinatorDr. Jan Raineyen_US
dc.contributor.thesis-readerDr. Barbara Kartenen_US
dc.contributor.thesis-readerDr. Paola Marignanien_US
dc.contributor.thesis-readerDr. Roger McLeoden_US
dc.contributor.thesis-supervisorDr. Petra Kienesbergeren_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsNot Applicableen_US
dc.contributor.copyright-releaseNot Applicableen_US
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