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.
journal_name
Elifejournal_title
eLifeauthors
Sharma A,Oonthonpan L,Sheldon RD,Rauckhorst AJ,Zhu Z,Tompkins SC,Cho K,Grzesik WJ,Gray LR,Scerbo DA,Pewa AD,Cushing EM,Dyle MC,Cox JE,Adams C,Davies BS,Shields RK,Norris AW,Patti G,Zingman LV,Taylor EBdoi
10.7554/eLife.45873subject
Has Abstractpub_date
2019-07-18 00:00:00issn
2050-084Xpii
45873journal_volume
8pub_type
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