Introduction
Bed-rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism(1). However, little is known about metabolic adaptation from acute to chronic BR, particularly when volunteers are maintained in energy balance. We therefore determined whole body GD, carbohydrate (CHO) and lipid oxidation and intramyocellular lipid (IMCL) content during acute and chronic BR whilst maintaining energy balance.
Method
Healthy males (n=10, 24±1.25 years, body mass index (BMI) 22.7±0.60) maintained in energy balance underwent 3 days of BR (acute BR; ABR). A second cohort matched for gender and body mass index (n=20, 34±1.8 years, 23.8±0.41) underwent 56 days of BR (chronic BR; CBR). An isoenergetic diet was maintained throughout both studies (30% fat,15% protein,55% CHO). A hyperinsulinaemic euglycaemic clamp (60 mU/kg body mass/min)was performed before and after BR. Indirect calorimetry was performed before and during the clamp steady-state to calculate rates of whole-body fuel oxidation. Vastus Lateralis muscle biopsies were taken before and after each clamp to quantify muscle glycogen content. Intramyocellular lipid (IMCL) content and expression levels of 191 mRNA targets were also determined in biopsy samples obtained before each clamp. Two-way repeated measures ANOVA was used to detect differences in end-point measures and Ingenuity Pathway Analysis was used to interrogate mRNA expression changes. All values presented are mean ± SEM.
Results
ABR reduced insulin-mediated glucose disposal (GD, normalised to DEXA determined lean body mass; LBM) by 17% (11.5 ± 0.7 vs 9.3 ± 0.6 mg/kg LBM/min; p<0.001). CBR reduced GD by 22% (10.2 ± 0.4 vs 7.9 ± 0.3 mg/kg LBM/min, p<0.05). This reduction in GD following both ABR and CBR was paralleled by the elimination of a 35% increase in insulin-stimulated muscle glycogen storage seen before BR. ABR had no impact on insulin-stimulated carbohydrate (CHO) and lipid oxidation, but CBR reduced CHO oxidation (p<0.05) and blunted the magnitude of insulin-mediated inhibition of lipid oxidation (p<0.05). Neither ABR nor CBR increased muscle intramyocellular lipid content. Plentiful mRNA abundance changes from before BR were detected following ABR, which had waned following CBR and generally reflected the changes in fuel oxidation and muscle glycogen storage seen at this time point.
Conclusion
ABR suppressed insulin-stimulated GD and glycogen storage, and the extent of suppression was increased no further after CBR. However, insulin-mediated inhibition of fat oxidation after CBR was less than after ABR, and was accompanied by blunted CHO oxidation. Moreover, this shift in substrate oxidation after CBR was not explained by IMCL accumulation, but was reflected by muscle mRNA abundance changes, pointing to the lack of muscle contraction per seas the primary signal for the adaptations observed.
Biomedical Basis of Elite Performance 2022 (University of Nottingham, UK) (2022) Proc Physiol Soc 49, SA17
Research Symposium: Muscle Insulin resistance and fuel metabolism in response to inactivity.
Natalie Shur1,2, Elizabeth Simpson2,3, Hannah Crossland2,3, Prince K. Chivaka4, Despina Constantin2,3, Sally M Cordon3, Dumitru Constantin-Teodosiu 3, Francis Stephens5, Dileep N Lobo2,6, Nate Szewczyk2,3,7, Marco Narici3, Clara Prats8, Ian MacDonald2,3,
1 Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH 2 National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH 3 MRC/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH 4 Centre for Sports, Exercise and Osteoarthritis Research Versus Arthritis 5 Sport and Health Sciences, The University of Exeter, Exeter, EX1 2LU, UK. 6 MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham National Institute for Health Research (NIHR) Biomedical Research Centre (BRC); 7 Ohio Musculoskeletal and Neurological Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 4570 8 Core Facility for Integrated Microscopy, The University of Copenhagen, Blegdamsvej 3, 2200 København N, 7.2, Building: 55, Denmark.
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Where applicable, experiments conform with Society ethical requirements.