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Ciaran Fealy Dissertation revised.pdf (3.45 MB)

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Insulin resistance in Obesity: Targeting the Molecular Mechanisms of Metabolic Disease

Fealy, Ciaran E
http://rave.ohiolink.edu/etdc/view?acc_num=kent1460740841

Abstract Details

2016, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
The prevalence of obesity has been increasing rapidly over the past 30 years such that obesity-associated metabolic diseases including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are now among the leading causes of morbidity and mortality. This makes the discovery of novel, practical therapies for prevention and treatment, along with better understanding of the mechanisms that link obesity to metabolic disease, the most significant challenge for biomedical research in the 21st century. Insulin resistance is a common pathology underlying the development of obesity associated metabolic disease and is a target for disease progression. Exercise has long been recognized as an effective tool for managing glycemic control and its use in research provides insight into the mechanisms that contribute to insulin resistance. We used an exercise approach to investigate the effect of exercise training, independent of weight loss, on markers of hepatocyte apoptosis in individuals with NAFLD. Our data indicate that hepatocyte apoptosis is reduced following 7 days of exercise training. We also examined the efficacy of a novel high intensity exercise program for improving insulin sensitivity and reducing cardiometabolic risk in T2D. We concluded that CrossFit exercise reduces insulin resistance and cardiovascular risk in T2D. We also used an exercise approach to investigate a novel target that may link mitochondrial dysfunction to insulin resistance. We demonstrated that the activation of the mitochondrial fission mediator dynamin-related protein-1 was reduced by exercise in insulin resistant muscle and subsequent cell culture experiments provide evidence that this may be linked to improvements in insulin signalling and mitochondrial coupling efficiency.
John Kirwan, PhD (Advisor)
Robert Dorman, PhD (Committee Chair)
Colleen Novak, PhD (Committee Member)
John Gunstad, MD (Committee Member)
Vijayaraghavan S, PhD (Committee Member)
207 p.
Biomedical Research; Cellular Biology; Endocrinology; Health Sciences; Kinesiology; Molecular Biology
Insulin Resistance; Obesity; NAFLD; Type 2 Diabetes; Exercise; Mitochondrial Dynamics; Mitochondrial Fission

Recommended Citations

Citations

  • Fealy, C. E. (2016). Insulin resistance in Obesity: Targeting the Molecular Mechanisms of Metabolic Disease [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1460740841

    APA Style (7th edition)

  • Fealy, Ciaran. Insulin resistance in Obesity: Targeting the Molecular Mechanisms of Metabolic Disease. 2016. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1460740841.

    MLA Style (8th edition)

  • Fealy, Ciaran. "Insulin resistance in Obesity: Targeting the Molecular Mechanisms of Metabolic Disease." Doctoral dissertation, Kent State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1460740841

    Chicago Manual of Style (17th edition)

kent1460740841
1,793
© 2016, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.