PMID- 30153068
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20200309
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 315
IP  - 5
DP  - 2018 Nov 1
TI  - Defining the contribution of skeletal muscle pyruvate dehydrogenase alpha1 to 
      exercise performance and insulin action.
PG  - E1034-E1045
LID - 10.1152/ajpendo.00241.2018 [doi]
AB  - The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is 
      an important control point for carbohydrate (CHO) oxidation. However, the 
      importance of the PDC and CHO oxidation to muscle metabolism and exercise 
      performance, particularly during prolonged or high-intensity exercise, has not 
      been fully defined especially in mature skeletal muscle. To this end, we 
      determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 
      1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy 
      metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) 
      feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout 
      (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in 
      adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile 
      performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) 
      littermates. Additionally, we studied glucose homeostasis and insulin sensitivity 
      in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHalpha in 
      skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, 
      muscle contractile function, or low-intensity exercise performance. Additionally, 
      there were no differences in muscle insulin sensitivity or body composition in 
      PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise 
      capacity during high-intensity exercise was severely impaired in PDHmKO mice, in 
      parallel with a large increase in plasma lactate concentration. In conclusion, 
      although skeletal muscle PDC is not a major contributor to resting energy 
      expenditure or long-duration, low-intensity exercise performance, it is necessary 
      for optimal performance during high-intensity exercise.
FAU - Svensson, Kristoffer
AU  - Svensson K
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
FAU - Dent, Jessica R
AU  - Dent JR
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
FAU - Tahvilian, Shahriar
AU  - Tahvilian S
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
FAU - Martins, Vitor F
AU  - Martins VF
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
FAU - Sathe, Abha
AU  - Sathe A
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
FAU - Ochala, Julien
AU  - Ochala J
AD  - School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, 
      King's College London , London , United Kingdom.
FAU - Patel, Mulchand S
AU  - Patel MS
AD  - Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, 
      University at Buffalo , Buffalo, New York.
FAU - Schenk, Simon
AU  - Schenk S
AD  - Department of Orthopaedic Surgery, University of California San Diego , La Jolla, 
      California.
AD  - Biomedical Sciences Graduate Program, University of California San Diego , La 
      Jolla, California.
LA  - eng
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - R01 AG043120/AG/NIA NIH HHS/United States
GR  - T32 GM007198/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180828
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Insulin)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 1.2.4.1 (Pyruvate Dehydrogenase (Lipoamide))
RN  - EC 1.2.4.1 (pyruvate dehydrogenase E1alpha subunit)
RN  - IY9XDZ35W2 (Glucose)
MH  - Adaptation, Physiological/physiology
MH  - Animals
MH  - Athletic Performance/*physiology
MH  - Body Composition/physiology
MH  - Diet, High-Fat
MH  - Energy Metabolism/physiology
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Tolerance Test
MH  - Insulin/*metabolism
MH  - Insulin Resistance/physiology
MH  - Lactic Acid/blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria, Muscle/metabolism
MH  - Muscle Contraction/physiology
MH  - Muscle, Skeletal/*metabolism
MH  - Oxygen Consumption/physiology
MH  - Physical Conditioning, Animal/*physiology
MH  - Pyruvate Dehydrogenase (Lipoamide)/genetics/*metabolism
PMC - PMC6293170
OTO - NOTNLM
OT  - contraction
OT  - exercise training
OT  - glucose metabolism
OT  - high-fat diet
OT  - mitochondria
EDAT- 2018/08/29 06:00
MHDA- 2019/08/27 06:00
PMCR- 2019/11/01
CRDT- 2018/08/29 06:00
PHST- 2018/08/29 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2018/08/29 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - E-00241-2018 [pii]
AID - 10.1152/ajpendo.00241.2018 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2018 Nov 1;315(5):E1034-E1045. doi: 
      10.1152/ajpendo.00241.2018. Epub 2018 Aug 28.