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

Available for download on Sunday, January 31, 2021

Included in

Biochemistry Commons

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