The impact of bed rest on human skeletal muscle metabolism

Moritz Eggelbusch; Braeden T Charlton; Alessandra Bosutti; Bergita Ganse; Ifigenia Giakoumaki; Anita E Grootemaat; Paul W Hendrickse; Yorrick Jaspers; Stephan Kemp; Tom J Kerkhoff; Wendy Noort; Michel van Weeghel; Nicole N van der Wel; Julia R Wesseling; Petra Frings-Meuthen; Jörn Rittweger; Edwin R Mulder; Richard T Jaspers; Hans Degens; Rob C I Wüst

doi:10.1016/j.xcrm.2023.101372

The impact of bed rest on human skeletal muscle metabolism

Moritz Eggelbusch, Braeden T Charlton, Alessandra Bosutti, Bergita Ganse, Ifigenia Giakoumaki, Anita E Grootemaat, Paul W Hendrickse, Yorrick Jaspers, Stephan Kemp, Tom J Kerkhoff, Wendy Noort, Michel van Weeghel, Nicole N van der Wel, Julia R Wesseling, Petra Frings-Meuthen, Jörn Rittweger, Edwin R Mulder, Richard T Jaspers, Hans Degens, Rob C I Wüst

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

Original language	English
Article number	101372
Pages (from-to)	101372
Journal	Cell reports. Medicine
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/j.xcrm.2023.101372
Publication status	Published - 16 Jan 2024

Bibliographical note

Funding

The authors acknowledge the support of the European Space Agency (ESA, grant number 16-16ESA AGBR-0013 , contract number 4000113871/15/NL/PG) and the National Aeronautics and Space Administration (NASA, grant number 80JSC018P0078). B.G. is supported by the German Research Foundation (grant number GA2420/1-1 ) and German Aerospace Center (grant number 50WB1928 ). A.B. is supported by the Italian Space Agency grant (MIAG project ASI n.2021-13-U.0). H.D., I.G., and P.H. are supported by the UK Space Agency ( ST/S0001735/1 and ST/T00066X/1 ). M.E. and R.C.I.W. are supported by an Amsterdam Movement Sciences PhD fellowship grant (2019). ESA and NASA were involved in the overall study design but not in the collection, data analysis and interpretation, the writing of the report, or the decision to submit the article for publication. The authors would like to thank Dr. Angelique van Ombergen for her assistance with ESA bed rest data sharing. Illustrations were created with BioRender.com (full license).

Funders	Funder number
National Aeronautics and Space Administration	80JSC018P0078
UK Space Agency	ST/T00066X/1, ST/S0001735/1
European Space Agency	4000113871/15/NL/PG, 16-16ESA AGBR-0013
Deutsche Forschungsgemeinschaft	GA2420/1-1
Deutsches Zentrum für Luft- und Raumfahrt	50WB1928
Agenzia Spaziale Italiana	ASI n.2021-13-U.0

Keywords

Humans
Insulin Resistance/physiology
Bed Rest/adverse effects
Muscle, Skeletal/metabolism
Energy Metabolism/physiology
Glycogen/metabolism

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Eggelbusch, M., Charlton, B. T., Bosutti, A., Ganse, B., Giakoumaki, I., Grootemaat, A. E., Hendrickse, P. W., Jaspers, Y., Kemp, S., Kerkhoff, T. J., Noort, W., van Weeghel, M., van der Wel, N. N., Wesseling, J. R., Frings-Meuthen, P., Rittweger, J., Mulder, E. R., Jaspers, R. T., Degens, H., & Wüst, R. C. I. (2024). The impact of bed rest on human skeletal muscle metabolism. Cell reports. Medicine, 5(1), 101372. Article 101372. https://doi.org/10.1016/j.xcrm.2023.101372

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abstract = "Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.",

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Eggelbusch, M, Charlton, BT, Bosutti, A, Ganse, B, Giakoumaki, I, Grootemaat, AE, Hendrickse, PW, Jaspers, Y, Kemp, S, Kerkhoff, TJ, Noort, W, van Weeghel, M, van der Wel, NN, Wesseling, JR, Frings-Meuthen, P, Rittweger, J, Mulder, ER, Jaspers, RT, Degens, H & Wüst, RCI 2024, 'The impact of bed rest on human skeletal muscle metabolism', Cell reports. Medicine, vol. 5, no. 1, 101372, pp. 101372. https://doi.org/10.1016/j.xcrm.2023.101372

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AU - Eggelbusch, Moritz

AU - Charlton, Braeden T

AU - Bosutti, Alessandra

AU - Ganse, Bergita

AU - Giakoumaki, Ifigenia

AU - Grootemaat, Anita E

AU - Hendrickse, Paul W

AU - Jaspers, Yorrick

AU - Kemp, Stephan

AU - Kerkhoff, Tom J

AU - Noort, Wendy

AU - van Weeghel, Michel

AU - van der Wel, Nicole N

AU - Wesseling, Julia R

AU - Frings-Meuthen, Petra

AU - Rittweger, Jörn

AU - Mulder, Edwin R

AU - Jaspers, Richard T

AU - Degens, Hans

AU - Wüst, Rob C I

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N2 - Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

AB - Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

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KW - Insulin Resistance/physiology

KW - Bed Rest/adverse effects

KW - Muscle, Skeletal/metabolism

KW - Energy Metabolism/physiology

KW - Glycogen/metabolism

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DO - 10.1016/j.xcrm.2023.101372

M3 - Article

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SN - 2666-3791

VL - 5

SP - 101372

JO - Cell reports. Medicine

JF - Cell reports. Medicine

IS - 1

M1 - 101372

ER -

The impact of bed rest on human skeletal muscle metabolism

Abstract

Bibliographical note

Funding

Keywords

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