PMID- 22315317
OWN - NLM
STAT- MEDLINE
DCOM- 20120628
LR  - 20220410
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 61
IP  - 5
DP  - 2012 May
TI  - The role of FOXO and PPAR transcription factors in diet-mediated inhibition of 
      PDC activation and carbohydrate oxidation during exercise in humans and the role 
      of pharmacological activation of PDC in overriding these changes.
PG  - 1017-24
LID - 10.2337/db11-0799 [doi]
AB  - High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled 
      carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We 
      aimed to reveal molecular changes underpinning this process in resting and 
      exercising humans. We also tested whether pharmacological activation of PDC 
      overrides these diet-induced changes. Healthy males consumed a control diet (CD) 
      and on two further occasions an isocaloric high-fat diet (HFD). After each diet, 
      subjects cycled for 60 min after intravenous infusion with saline (CD and HFD) or 
      dichloroacetate (HFD+DCA). Quadriceps muscle biopsies obtained before and after 
      10 and 60 min of exercise were used to estimate CHO use, PDC activation, and 
      mRNAs associated with insulin, fat, and CHO signaling. Compared with CD, HFD 
      increased resting pyruvate dehydrogenase kinase 2 (PDK2), PDK4, forkhead box 
      class O transcription factor 1 (FOXO1), and peroxisome proliferator-activated 
      receptor transcription factor alpha (PPARalpha) mRNA and reduced PDC activation. Exercise 
      increased PDC activation and whole-body CHO use in HFD, but to a lower extent 
      than in CD. Meanwhile PDK4 and FOXO1, but not PPARalpha or PDK2, mRNA remained 
      elevated. HFD+DCA activated PDC throughout and restored whole-body CHO use during 
      exercise. FOXO1 appears to play a role in HFD-mediated muscle PDK4 upregulation 
      and inhibition of PDC and CHO oxidation in humans. Also, pharmacological 
      activation of PDC restores HFD-mediated inhibition of CHO oxidation during 
      exercise.
FAU - Constantin-Teodosiu, Dumitru
AU  - Constantin-Teodosiu D
AD  - School of Biomedical Sciences, Medical School, University of Nottingham, 
      Nottingham, UK. tim.constantin@nottingham.ac.uk
FAU - Constantin, Despina
AU  - Constantin D
FAU - Stephens, Francis
AU  - Stephens F
FAU - Laithwaite, David
AU  - Laithwaite D
FAU - Greenhaff, Paul L
AU  - Greenhaff PL
LA  - eng
GR  - MR/K00414X/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20120207
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Dietary Fats)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (PPAR alpha)
RN  - 0 (Pyruvate Dehydrogenase Complex)
RN  - 0 (RNA, Messenger)
RN  - 9LSH52S3LQ (Dichloroacetic Acid)
SB  - IM
CIN - Diabetes. 2012 May;61(5):983. PMID: 22517651
MH  - Adult
MH  - Carbohydrate Metabolism/*physiology
MH  - Dichloroacetic Acid/administration & dosage/pharmacology
MH  - *Diet
MH  - Dietary Fats/pharmacology
MH  - Exercise/*physiology
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/genetics/*metabolism
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Humans
MH  - Male
MH  - Muscle, Skeletal/metabolism
MH  - Oxidation-Reduction
MH  - PPAR alpha/genetics/*metabolism
MH  - Pyruvate Dehydrogenase Complex/*metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC3331777
EDAT- 2012/02/09 06:00
MHDA- 2012/06/29 06:00
PMCR- 2013/05/01
CRDT- 2012/02/09 06:00
PHST- 2012/02/09 06:00 [entrez]
PHST- 2012/02/09 06:00 [pubmed]
PHST- 2012/06/29 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - db11-0799 [pii]
AID - 0799 [pii]
AID - 10.2337/db11-0799 [doi]
PST - ppublish
SO  - Diabetes. 2012 May;61(5):1017-24. doi: 10.2337/db11-0799. Epub 2012 Feb 7.