PMID- 36058634
OWN - NLM
STAT- MEDLINE
DCOM- 20221214
LR  - 20230315
IS  - 2190-6009 (Electronic)
IS  - 2190-5991 (Print)
IS  - 2190-5991 (Linking)
VI  - 13
IP  - 6
DP  - 2022 Dec
TI  - Human adaptation to immobilization: Novel insights of impacts on glucose disposal 
      and fuel utilization.
PG  - 2999-3013
LID - 10.1002/jcsm.13075 [doi]
AB  - BACKGROUND: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal 
      (GD) and alters muscle fuel metabolism, but little is known about metabolic 
      adaptation from acute to chronic BR nor the mechanisms involved, particularly 
      when volunteers are maintained in energy balance. METHODS: Healthy males (n = 10, 
      24.0 +/- 1.3 years), maintained in energy balance, underwent 3-day BR (acute BR). A 
      second cohort matched for sex and body mass index (n = 20, 34.2 +/- 1.8 years) 
      underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp 
      (60 mU/m(2) /min) was performed to determine rates of whole-body 
      insulin-stimulated GD before and after BR (normalized to lean body mass). 
      Indirect calorimetry was performed before and during steady state of each clamp 
      to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to 
      determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, 
      and the expression of 191 mRNA targets before and after BR. Two-way repeated 
      measures analysis of variance was used to detect differences in endpoint 
      measures. RESULTS: Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 
      9.3 +/- 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following 
      chronic BR (Pre 10.2 +/- 0.4 vs. Post 7.9 +/- 0.3 mg/kg/min, P < 0.05). This 
      reduction in GD was paralleled by the elimination of the 35% increase in 
      insulin-stimulated muscle glycogen storage following both acute and chronic BR. 
      Acute BR had no impact on insulin-stimulated carbohydrate (CHO; Pre 3.69 +/- 0.39 
      vs. Post 4.34 +/- 0.22 mg/kg/min) and lipid (Pre 1.13 +/- 0.14 vs. Post 
      0.59 +/- 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 
      3.34 +/- 0.18 vs. Post 2.72 +/- 0.13 mg/kg/min, P < 0.05) and blunted the magnitude 
      of insulin-mediated inhibition of lipid oxidation (Pre 0.60 +/- 0.07 vs. Post 
      0.85 +/- 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle 
      IMCL content. Plentiful mRNA abundance changes were detected following acute BR, 
      which waned following chronic BR and reflected changes in fuel oxidation and 
      muscle glycogen storage at this time point. CONCLUSIONS: Acute BR suppressed 
      insulin-stimulated GD and storage, but the extent of this suppression increased 
      no further in chronic BR. However, insulin-mediated inhibition of fat oxidation 
      after chronic BR was less than acute BR and was accompanied by blunted CHO 
      oxidation. The juxtaposition of these responses shows that the regulation of GD 
      and storage can be dissociated from substrate oxidation. Additionally, the shift 
      in substrate oxidation after chronic BR was not explained by IMCL accumulation 
      but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein 
      abundance changes, pointing to lack of muscle contraction per se as the primary 
      signal for muscle adaptation.
CI  - (c) 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John 
      Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting 
      Disorders.
FAU - Shur, Natalie F
AU  - Shur NF
AUID- ORCID: 0000-0002-6622-2525
AD  - Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School 
      of Life Sciences, The University of Nottingham, Nottingham, UK.
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
FAU - Simpson, Elizabeth J
AU  - Simpson EJ
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Crossland, Hannah
AU  - Crossland H
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Chivaka, Prince K
AU  - Chivaka PK
AD  - Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School 
      of Life Sciences, The University of Nottingham, Nottingham, UK.
FAU - Constantin, Despina
AU  - Constantin D
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Cordon, Sally M
AU  - Cordon SM
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Constantin-Teodosiu, Dumitru
AU  - Constantin-Teodosiu D
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Stephens, Francis B
AU  - Stephens FB
AD  - Sport and Health Sciences, The University of Exeter, Exeter, UK.
FAU - Lobo, Dileep N
AU  - Lobo DN
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Szewczyk, Nate
AU  - Szewczyk N
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
AD  - Ohio Musculoskeletal and Neurological Institute, Heritage College of Osteopathic 
      Medicine, Ohio University, Athens, OH, USA.
FAU - Narici, Marco
AU  - Narici M
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
AD  - Department of Biomedical Sciences, University of Padua, Padua, Italy.
FAU - Prats, Clara
AU  - Prats C
AD  - Core Facility for Integrated Microscopy, The University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Macdonald, Ian A
AU  - Macdonald IA
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
FAU - Greenhaff, Paul L
AU  - Greenhaff PL
AD  - Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School 
      of Life Sciences, The University of Nottingham, Nottingham, UK.
AD  - National Institute for Health and Care Research (NIHR) Nottingham Biomedical 
      Research Centre, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, UK.
AD  - MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life 
      Sciences and Medicine, University of Nottingham, Nottingham, UK.
LA  - eng
GR  - MR/P021220/1/MRC_/Medical Research Council/United Kingdom
GR  - BB/P005004/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220904
PL  - Germany
TA  - J Cachexia Sarcopenia Muscle
JT  - Journal of cachexia, sarcopenia and muscle
JID - 101552883
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Insulin)
RN  - 9005-79-2 (Glycogen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Lipids)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Glucose/metabolism
MH  - *Muscle, Skeletal/metabolism
MH  - Insulin/metabolism
MH  - Glycogen/metabolism
MH  - RNA, Messenger/metabolism
MH  - Lipids
PMC - PMC9745545
OTO - NOTNLM
OT  - bed rest
OT  - fuel oxidation
OT  - insulin resistance
OT  - muscle metabolism
COIS- None declared.
EDAT- 2022/09/05 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/01
CRDT- 2022/09/04 21:32
PHST- 2022/06/21 00:00 [revised]
PHST- 2021/09/09 00:00 [received]
PHST- 2022/08/14 00:00 [accepted]
PHST- 2022/09/05 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/09/04 21:32 [entrez]
PHST- 2022/12/01 00:00 [pmc-release]
AID - JCSM13075 [pii]
AID - 10.1002/jcsm.13075 [doi]
PST - ppublish
SO  - J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2999-3013. doi: 10.1002/jcsm.13075. 
      Epub 2022 Sep 4.