Journal article
Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness
eLife, Vol.8, e45873
07/18/2019
DOI: 10.7554/eLife.45873
PMCID: PMC6684275
PMID: 31305240
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 diverted pyruvate into circulating lactate. This switch disinhibited muscle fatty acid oxidation and drove Cori Cycling that contributed to increased energy expenditure. Loss of muscle MPC activity led to strikingly decreased adiposity with complete muscle mass and strength retention. Notably, despite decreasing muscle glucose oxidation, muscle MPC disruption increased muscle glucose uptake and whole-body insulin sensitivity. 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 whole-body carbon flux control point. They highlight the potential utility of modulating muscle pyruvate utilization to ameliorate obesity and type 2 diabetes.
Details
- Title: Subtitle
- Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness
- Creators
- Arpit Sharma - Roy J. and Lucille A. Carver College of MedicineLalita Oonthonpan - Roy J. and Lucille A. Carver College of MedicineRyan D Sheldon - University of IowaAdam J Rauckhorst - University of IowaZhiyong Zhu - University of IowaSean C Tompkins - Roy J. and Lucille A. Carver College of MedicineKevin Cho - Washington University in St. LouisWojciech J Grzesik - University of IowaLawrence R Gray - Roy J. and Lucille A. Carver College of MedicineDiego A Scerbo - Roy J. and Lucille A. Carver College of MedicineAlvin D Pewa - University of IowaEmily M Cushing - Roy J. and Lucille A. Carver College of MedicineMichael C Dyle - Roy J. and Lucille A. Carver College of MedicineJames E Cox - University of UtahChris Adams - University of IowaBrandon S Davies - University of IowaRichard K Shields - University of IowaAndrew W Norris - University of IowaGary Patti - Washington University in St. LouisLeonid V Zingman - University of IowaEric B Taylor - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.8, e45873
- DOI
- 10.7554/eLife.45873
- PMID
- 31305240
- PMCID
- PMC6684275
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- DK104998 / NIH HHS R01 DK104998 / NIDDK NIH HHS AR059190 / NIH HHS GM007337 / NIH HHS DK116522 / NIH HHS 1-18-PDF-060 / American Diabetes Association T32 GM007337 / NIGMS NIH HHS DK092412 / NIH HHS R00 AR059190 / NIAMS NIH HHS HL007344 / NIH HHS HL007638 / NIH HHS HL130146 / NIH HHS T32 HL007344 / NHLBI NIH HHS ES028365 / NIH HHS HD082109 / NIH HHS HD084645 / NIH HHS P30 DK054759 / NIDDK NIH HHS DK101183 / NIH HHS DK112751 / NIH HHS
- Language
- English
- Date published
- 07/18/2019
- Academic Unit
- Molecular Physiology and Biophysics; Endocrinology and Diabetes; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984293086702771
Metrics
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