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    Heat Shock Proteins: Treating Metabolic Disease by Turning up the Heat

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    Rogers_ku_0099D_14362_DATA_1.pdf (4.157Mb)
    Issue Date
    2015-12-31
    Author
    Rogers, Robert Steven
    Publisher
    University of Kansas
    Format
    185 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Molecular & Integrative Physiology
    Rights
    Copyright held by the author.
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    Abstract
    The prevalence of type 2 diabetes has risen as access to nutrition as increased and physical activity levels have decreased. Low cardiorespiratory fitness (CRF) levels are influenced by genetics, but low levels of physical activity also drive down levels of CRF in individuals increasing their susceptibility to metabolic disease. Heat shock proteins (HSP) are anti-inflammatory, anti-apoptotic molecular chaperones that assist in refolding proteins that have become unfolded during stress. HSP72 expression is lower in multiple tissues of obese, type 2 diabetics and HSP72 ablation results in insulin resistance. The work here confirms that in vivo heat treatments and the induction of HSP72 improve whole-body glucose homeostasis, skeletal muscle insulin sensitivity, and suggest that heat treatment may protect against metabolic derangements in the white adipose tissue and liver. In the WAT, constitutive HSP levels and the induction of HSPs following heat treatment is different between WAT depots with abdominal WAT showing greater constitutive HSP levels but a lower induction of HSPs following heat treatment. Heat treatment also modified fatty acid handling in the WAT in a depot specific fashion. Using a rat model to mimic intrinsic low CRF observed in diabetic humans, we examine the metabolism of rats selectively bred to be low capacity runners (LCR) or high capacity runners (HCR). We observed that LCR rats a particular susceptible to skeletal muscle insulin resistance following an acute (3 d) high-fat diet challenge, particularly in the glycolytic muscle where we observed lower HSF-1, HSP72, and mitochondrial proteins. In the liver and skeletal muscle, a 3 d HFD reduced the induction of HSPs following heat treatment. Finally, we found evidence that supports a role for HSP72 in maintaining proper autophagy-mitophagy that may result in an improved pool of functional mitochondria. This work strongly suggests that that HSP72 plays a role in protection against insulin resistance and metabolic derangements induced by high-fat feeding in multiple organs intimately tied with whole-body glucose homeostasis.
    URI
    http://hdl.handle.net/1808/23940
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    • KU Med Center Dissertations and Theses [464]
    • Dissertations [4320]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
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    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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