PMID- 32824862
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210317
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 16
DP  - 2020 Aug 18
TI  - PPARdelta and FOXO1 Mediate Palmitate-Induced Inhibition of Muscle Pyruvate 
      Dehydrogenase Complex and CHO Oxidation, Events Reversed by Electrical Pulse 
      Stimulation.
LID - 10.3390/ijms21165942 [doi]
LID - 5942
AB  - The mechanisms behind the reduction in muscle pyruvate dehydrogenase complex 
      (PDC)-controlled carbohydrate (CHO) oxidation during chronic high-fat dietary 
      intake are poorly understood, as is the basis of CHO oxidation restoration during 
      muscle contraction. C2C12 myotubes were treated with (300 muM) palmitate or 
      without (control) for 16 h in the presence and absence of electrical pulse 
      stimulation (EPS, 11.5 V, 1 Hz, 2 ms). Compared to control, palmitate reduced 
      cell glucose uptake (p < 0.05), PDC activity (p < 0.01), acetylcarnitine 
      accumulation (p < 0.05) and glucose-derived mitochondrial ATP production (p < 
      0.01) and increased pyruvate dehydrogenase kinase isoform 4 (PDK4) (p < 0.01), 
      peroxisome proliferator-activated receptor alpha (PPARalpha) (p < 0.01) and 
      peroxisome proliferator-activated receptor delta (PPARdelta) (p < 0.01) proteins, and 
      reduced the whole-cell p-FOXO1/t-FOXO1 (Forkhead Box O1) ratio (p < 0.01). EPS 
      rescued palmitate-induced inhibition of CHO oxidation, reflected by increased 
      glucose uptake (p < 0.01), PDC activity (p < 0.01) and glucose-derived 
      mitochondrial ATP production (p < 0.01) compared to palmitate alone. EPS was also 
      associated with less PDK4 (p < 0.01) and PPARdelta (p < 0.01) proteins, and lower 
      nuclear p-FOXO1/t-FOXO1 ratio normalised to the cytoplasmic ratio, but with no 
      changes in PPARalpha protein. Collectively, these data suggest PPARdelta, and FOXO1 
      transcription factors increased PDK4 protein in the presence of palmitate, which 
      limited PDC activity and flux, and blunted CHO oxidation and glucose uptake. 
      Conversely, EPS rescued these metabolic events by modulating the same 
      transcription factors.
FAU - Chien, Hung-Che
AU  - Chien HC
AUID- ORCID: 0000-0002-2500-0299
AD  - School of Life Sciences, University of Nottingham, Queen's Medical Centre, 
      Nottingham NG7 2UH, UK.
AD  - Department of Physiology and Biophysics, National Defense Medical Centre, Taipei 
      11490, Taiwan.
FAU - Greenhaff, Paul L
AU  - Greenhaff PL
AD  - School of Life Sciences, University of Nottingham, Queen's Medical Centre, 
      Nottingham NG7 2UH, UK.
FAU - Constantin-Teodosiu, Dumitru
AU  - Constantin-Teodosiu D
AD  - School of Life Sciences, University of Nottingham, Queen's Medical Centre, 
      Nottingham NG7 2UH, UK.
LA  - eng
GR  - MR/K00414X/1/MRC_/Medical Research Council/United Kingdom
GR  - 19891/ARC_/Arthritis Research UK/United Kingdom
GR  - xxxxx/National Defense Medical Centre, Taipei 11490, Taiwan/
GR  - MR/K00414X/1/Medical Research Council grant number/
PT  - Journal Article
DEP - 20200818
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Foxo1 protein, mouse)
RN  - 0 (PPAR delta)
RN  - 0 (Palmitates)
RN  - 0 (Pdk4 protein, mouse)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 6DH1W9VH8Q (Acetylcarnitine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Acetylcarnitine/metabolism
MH  - Action Potentials
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Line
MH  - Forkhead Box Protein O1/*metabolism
MH  - Glucose/*metabolism
MH  - Mice
MH  - Mitochondria, Muscle/metabolism
MH  - *Muscle Contraction
MH  - Muscle Fibers, Skeletal/drug effects/*metabolism/physiology
MH  - PPAR delta/*metabolism
MH  - Palmitates/pharmacology
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase/*metabolism
PMC - PMC7460628
OTO - NOTNLM
OT  - contraction
OT  - free fatty acids
OT  - insulin resistance
OT  - muscle cell
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/23 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/08/01
CRDT- 2020/08/23 06:00
PHST- 2020/07/20 00:00 [received]
PHST- 2020/08/07 00:00 [revised]
PHST- 2020/08/15 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - ijms21165942 [pii]
AID - ijms-21-05942 [pii]
AID - 10.3390/ijms21165942 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Aug 18;21(16):5942. doi: 10.3390/ijms21165942.