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Modulation of Metabolic Reprogramming in Macrophage Impacts the Pathogenesis of Insulin Resistance and Type II Diabetes

Ko, Chihwei
http://rave.ohiolink.edu/etdc/view?acc_num=case1480681093917857

Abstract Details

, Doctor of Philosophy, Case Western Reserve University, Nutrition.
The prevalence of Type II diabetes in U.S. is increasing every year. Type II diabetes is closely associated with the development of obesity as well as a chronic state of low-grade inflammation. Obesity is a result of energy imbalance between calories consumption and calories expense. Expansion of fat mass through enlargement of adipocytes promotes infiltration of macrophages into the adipose tissue. These adipose tissue resident macrophages consist of at least two different phenotypes, classically activated (M1) and alternatively activated (M2). In the adipose tissue of lean mice, the majority of macrophages are M2-like, whereas in patients with type II diabetes, M1-like predominate. In addition, the metabolism of M1 and M2 are significantly different; M1 macrophages primarily utilize glucose, while M2 macrophages primarily utilize fatty acids. We have discovered that phosphoenolpyruvate carboxykinase (Pck1) is expressed in macrophages. Pck1 has been well studied in various tissues with its role in the modulation of gluconeogenesis, glyceroneogenesis and anaplerosis pathways. To determine the role of Pck1 in macrophages, we generated mice with a myeloid-specific deletion of Pck1. From our mouse model, we found Pck1 is required for the anaplerosis pathway in M1 classically activated macrophages. Deletion of Pck1 in macrophages, moreover, promotes macrophage immune responses to LPS. As macrophages respond to homeostatic or inflammatory stimuli within the microenvironment of that tissue, we the assessed whole-body metabolic phenotypes in mice impacted by macrophages. Mice with deletion of Pck1 in macrophages exhibited improved glucose metabolism with reduced de novo lipogenesis. These observations provide an advantage physiological condition against the development of insulin resistance and type II diabetes.
Colleen Croniger (Advisor)
Danny Manor (Committee Chair)
Laura Nagy (Committee Member)
David Buchner (Committee Member)
David Lodowski (Committee Member)
Nutrition

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Citations

  • Ko, C. (n.d.). Modulation of Metabolic Reprogramming in Macrophage Impacts the Pathogenesis of Insulin Resistance and Type II Diabetes [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1480681093917857

    APA Style (7th edition)

  • Ko, Chihwei. Modulation of Metabolic Reprogramming in Macrophage Impacts the Pathogenesis of Insulin Resistance and Type II Diabetes. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1480681093917857.

    MLA Style (8th edition)

  • Ko, Chihwei. "Modulation of Metabolic Reprogramming in Macrophage Impacts the Pathogenesis of Insulin Resistance and Type II Diabetes." Doctoral dissertation, Case Western Reserve University. Accessed MAY 02, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1480681093917857

    Chicago Manual of Style (17th edition)

case1480681093917857
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.