Role of Ceramidase in Regulating Hepatic Lipid Metabolism and Whole Body Insulin Sensitivity

dc.contributor.advisorBickel, Perryen
dc.contributor.committeeMemberScherer, Philippen
dc.contributor.committeeMemberHolland, William L.en
dc.contributor.committeeMemberGoodman, Joel M.en
dc.contributor.committeeMemberHorton, Jay D.en
dc.creatorXia, Jonathan Y.en
dc.creator.orcid0000-0003-1003-9454
dc.date.accessioned2019-06-03T19:54:20Z
dc.date.available2019-06-03T19:54:20Z
dc.date.created2017-05
dc.date.issued2017-03-16
dc.date.submittedMay 2017
dc.date.updated2019-06-03T19:54:20Z
dc.description.abstractConcomitant with the rise in obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD), a newly emerging obesity-related disorder, has also been rising steadily. NAFLD is a chronic liver disease that ranges histologically from simple steatosis in its mildest form to non-alcoholic steatohepatitis (NASH) in the more severe form, which is characterized by hepatocyte inflammation and fibrosis. In recent years, sphingolipids have garnered increasing attention for their role in the development of diabetes and metabolic syndrome. Specifically, the accumulation of ceramides in liver was shown to be associated with both hepatic insulin resistance and NAFLD. We recently demonstrated that the adipose-derived secretory factor adiponectin promotes an increase in ceramide catabolism, which is dependent on adiponectin receptors 1 and 2. The associated ceramidase activity promotes ceramide degradation and generation of sphingosine 1-phosphate (S1P). To further investigate the tissue-specific effects of the receptor associated ceramidase activity, we have developed transgenic mice that inducibly express adiponectin receptors 1 and 2 under the control of a tetracycline response element. Hepatic overexpression of adiponectin receptors improved whole body glucose metabolism and prevented hepatic steatosis. Furthermore, we found that catabolism of hepatic ceramides improved insulin signaling in the adipocyte, which suggests the existence of a "cross-talk" between liver and adipose tissue.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1103324673
dc.identifier.urihttps://hdl.handle.net/2152.5/6598
dc.language.isoenen
dc.subjectAdipokinesen
dc.subjectCeramidasesen
dc.subjectCeramidesen
dc.subjectInsulin Resistanceen
dc.subjectLipid Metabolismen
dc.subjectReceptors, Adiponectinen
dc.titleRole of Ceramidase in Regulating Hepatic Lipid Metabolism and Whole Body Insulin Sensitivityen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineIntegrative Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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