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    The impact of bed rest on human skeletal muscle metabolism

    Eggelbusch, Moritz, Charlton, Braeden T, Bosutti, Alessandra, Ganse, Bergita, Giakoumaki, Ifigenia, Grootemaat, Anita E, Hendrickse, Paul W, Jaspers, Yorrick, Kemp, Stephan, Kerkhoff, Tom J, Noort, Wendy, van Weeghel, Michel, van der Wel, Nicole N, Wesseling, Julia R, Frings-Meuthen, Petra, Rittweger, Jörn, Mulder, Edwin R, Jaspers, Richard T, Degens, Hans ORCID logoORCID: https://orcid.org/0000-0001-7399-4841 and Wüst, Rob CI ORCID logoORCID: https://orcid.org/0000-0003-3781-5177 (2024) The impact of bed rest on human skeletal muscle metabolism. Cell Reports Medicine, 5 (1). 101372. ISSN 2666-3791

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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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