The impact of bed rest on human skeletal muscle metabolism

• Published in: Cell reports. Medicine Vol. 5; no. 1; p. 101372
• Main Authors: 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, Wüst, Rob C.I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.01.2024; Elsevier
• Subjects: Advanced Basic Science; bed rest; Bed Rest - adverse effects; Energy Metabolism - physiology; GLUT4; Glycogen - metabolism; Humans; Insulin Resistance - physiology; insulin sensitivity; lipotoxicity; metabolism; mitochondria; Muscle, Skeletal - metabolism; nutrient overload; physical inactivity; skeletal muscle; insulin sensitivity; bed rest; mitochondria; lipotoxicity; nutrient overload; metabolism; skeletal muscle; GLUT4; physical inactivity
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2023.101372

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. [Display omitted] •Muscle glycogen build-up in bed rest reduces insulin sensitivity and further storage•Muscle lipid overload, lipotoxicity, and inflammation develop during bed rest•Bed rest shifts muscle metabolism from fatty acid to glucose oxidation•Intrinsic mitochondrial alterations occur after long-term bed rest Eggelbusch et al. show that a bed rest-induced nutrient overload contributes to insulin insensitivity, lipotoxicity, and mitochondrial alterations in human skeletal muscle. During prolonged bed rest, rapid insulin insensitivity and a metabolic shift toward glucose oxidation minimize additional glycogen storage, while inherent mitochondrial alterations are linked to progressive lipid accumulation.