Iron Overload Reduces Adiponectin Receptor-1 Expression via a ROS/FOXO1-Dependent Mechanism Leading to Adiponectin Resistance in Skeletal Muscle Cells

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dc.contributor.advisorsweeney, gary
dc.contributor.authorDahyaleh, Karam
dc.date.accessioned2020-05-11T12:35:30Z
dc.date.available2020-05-11T12:35:30Z
dc.date.copyright2019-08
dc.date.issued2020-05-11
dc.date.updated2020-05-11T12:35:30Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractIron overload (IO) is a common yet underappreciated observation in metabolic syndrome (MetS) patients. With the prevalence of MetS continuing to rise, it is of utmost importance to further elucidate mechanisms leading to metabolic dysfunction. IO positively correlates with reduced circulating adiponectin levels yet the impact of IO on adiponectin action is unknown. Here, we established a model of IO in L6 skeletal muscle cells and found that it induced adiponectin resistance, measured by reduced P38 MAPK phosphorylation by the adiponectin receptor (AdipoR) agonist AdipoRon. This correlated with reduced mRNA and protein levels of AdipoR1 and its facilitative binding partner APPL1. IO caused phosphorylation, nuclear extrusion and inhibition of FOXO1, a known transcription factor for AdipoR1. Reactive oxygen species production was induced by IO and using N-acetyl cysteine (NAC) to prevent this attenuated the effect of IO in FOXO1 phosphorylation, localization and adiponectin resistance. In conclusion, our study identifies a ROS/FOXO1/AdipoR1 axis as a cause of skeletal muscle adiponectin resistance in response to IO. This new knowledge provides new insight on potential disease pathophysiology in MetS patients with IO.
dc.identifier.urihttps://hdl.handle.net/10315/37344
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectCellular biology
dc.subject.keywordsDiabetes
dc.subject.keywordsMetabolic disorders
dc.subject.keywordsIron overload
dc.subject.keywordsPhysiology
dc.titleIron Overload Reduces Adiponectin Receptor-1 Expression via a ROS/FOXO1-Dependent Mechanism Leading to Adiponectin Resistance in Skeletal Muscle Cells
dc.typeElectronic Thesis or Dissertation

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