DOI
10.17077/etd.bgjn-khw1
Document Type
Dissertation
Date of Degree
Fall 2018
Access Restrictions
Access restricted until 01/31/2021
Degree Name
PhD (Doctor of Philosophy)
Degree In
Biochemistry
First Advisor
Taylor, Eric B.
First Committee Member
Wallrath, Lori
Second Committee Member
Davies, Brandon
Third Committee Member
Rubenstein, Peter
Fourth Committee Member
Sivitz, William
Fifth Committee Member
Baker, Sheila
Abstract
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.
Keywords
Cori Cycle, Diabetes, Fatty acid oxidation, Metabolism, MPC, Muscle
Pages
xv, 155 pages
Bibliography
Includes bibliographical references (pages 139-155).
Copyright
Copyright © 2018 Arpit Sharma
Recommended Citation
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.
https://doi.org/10.17077/etd.bgjn-khw1