Maximal oxidative capacity during exercise is associated with skeletal muscle fuel selection and dynamic changes in mitochondrial protein acetylation.

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TitleMaximal oxidative capacity during exercise is associated with skeletal muscle fuel selection and dynamic changes in mitochondrial protein acetylation.
Publication TypeJournal Article
Year of Publication2015
AuthorsOvermyer KA, Evans CR, Qi NR, Minogue CE, Carson JJ, Chermside-Scabbo CJ, Koch LG, Britton SL, Pagliarini DJ, Coon JJ, Burant CF
JournalCell Metab
Volume21
Issue3
Pagination468-78
Date Published2015 Mar 3
ISSN1932-7420
Abstract

Maximal exercise-associated oxidative capacity is strongly correlated with health and longevity in humans. Rats selectively bred for high running capacity (HCR) have improved metabolic health and are longer-lived than their low-capacity counterparts (LCR). Using metabolomic and proteomic profiling, we show that HCR efficiently oxidize fatty acids (FAs) and branched-chain amino acids (BCAAs), sparing glycogen and reducing accumulation of short- and medium-chain acylcarnitines. HCR mitochondria have reduced acetylation of mitochondrial proteins within oxidative pathways at rest, and there is rapid protein deacetylation with exercise, which is greater in HCR than LCR. Fluxomic analysis of valine degradation with exercise demonstrates a functional role of differential protein acetylation in HCR and LCR. Our data suggest that efficient FA and BCAA utilization contribute to high intrinsic exercise capacity and the health and longevity benefits associated with enhanced fitness.

DOI10.1016/j.cmet.2015.02.007
Alternate JournalCell Metab.
PubMed ID25738461
PubMed Central IDPMC4350023
Grant ListK25 DK092558 / DK / NIDDK NIH HHS / United States
K25DK092558 / DK / NIDDK NIH HHS / United States
NLM T15LM007359 / / PHS HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
P30 DK089503 / DK / NIDDK NIH HHS / United States
R01 DK077200 / DK / NIDDK NIH HHS / United States
R01 DK098672 / DK / NIDDK NIH HHS / United States
R01 DK099034 / DK / NIDDK NIH HHS / United States
R01 GM080148 / GM / NIGMS NIH HHS / United States
R01DK077200 / DK / NIDDK NIH HHS / United States
R01DK098672 / DK / NIDDK NIH HHS / United States
R01DK099034 / DK / NIDDK NIH HHS / United States
R01GM080148 / GM / NIGMS NIH HHS / United States
R01GM104194 / GM / NIGMS NIH HHS / United States
R24 OD010950 / OD / NIH HHS / United States
R24DK097153 / DK / NIDDK NIH HHS / United States
R24OD010950 / OD / NIH HHS / United States
T15 LM007359 / LM / NLM NIH HHS / United States
U24 DK097153 / DK / NIDDK NIH HHS / United States