Date of Degree
Access restricted until 01/31/2021
PhD (Doctor of Philosophy)
Taylor, Eric B
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Fifth Committee Member
Metabolic cycles are a fundamental element of cellular and organismal function. Among the most critical in higher organisms is the Cori Cycle, the systemic cycling between lactate and glucose. Here, skeletal muscle-specific Mitochondrial Pyruvate Carrier (MPC) deletion in mice increased muscle glucose uptake but diverted pyruvate into the circulation as lactate, driving increased Cori Cycling and energy expenditure. Loss of muscle MPC activity evoked adaptive glutaminolysis, increased fatty acid oxidation, and resulted in a striking resistance to gains in fat mass with age with perfect sparing of muscle mass and strength. Furthermore, chronic and acute muscle MPC deletion accelerated fat mass loss on a normal diet after high fat diet-induced obesity. Our results illuminate the role of the skeletal muscle MPC as a central node for whole-body carbohydrate, fat, and amino acid metabolism. They highlight the potential utility of decreasing muscle pyruvate oxidation to ameliorate obesity and type 2 diabetes.
Cori Cycle, Diabetes, Fatty acid oxidation, Metabolism, MPC, Muscle
xv, 155 pages
Includes bibliographical references (pages 139-155).
Copyright © 2018 Arpit Sharma
Sharma, Arpit. "The role of the skeletal muscle mitochondrial pyruvate carrier in systemic glucose homeostasis and whole-body adiposity." PhD (Doctor of Philosophy) thesis, University of Iowa, 2018.
Available for download on Sunday, January 31, 2021