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Eggelbusch 2022 Abstract Bioblast

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7.1. «5 min»
Eggelbusch Moritz
Eggelbusch Moritz, Hendrickse P, Schoonen R, Giakoumaki I, Kerkhoff TJ, Grootemaat AE, Rittweger J, Ganse B, Weeghel van M, Mulder ER, Degens H, Wüst RCI (2022) Nutrient overload and insulin resistance precede reductions in mitochondrial respiration in skeletal muscle after bed rest.
Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001 »Watch the presentation«

Link: Bioblast 2022: BEC Inaugural Conference

Eggelbusch Moritz, Hendrickse P, Schoonen R, Giakoumaki I, Kerkhoff TJ, Grootemaat AE, Rittweger J, Ganse B, Weeghel van M, Mulder ER, Degens H, Wuest Rob CI (2022)

Event: Bioblast 2022

Physical inactivity contributes to insulin resistance and the development of type 2 diabetes [1]. Metabolic flexibility, the ability to efficiently adapt substrate oxidation depending on demand and supply, decreases in response to bed rest [1,2]. A mismatch between nutrient uptake and utilization rates likely underlies these metabolic alterations [3], but it is unknown if glycogen and lipid accumulation, or mitochondrial dysfunction occur before insulin resistance develops. Here, we determined nutrient load, insulin sensitivity, metabolite concentrations and mitochondrial function in skeletal muscle in humans undergoing short- and long-term bed rest, and assess the order of occurrence of events.

24 healthy individuals (23-54 years, 8 women) participated in the 60-days artificial gravity bed rest study by ESA (AGBRESA). Oroboros respirometry, metabolomics and lipidomics (on a subset) were performed on vastus lateralis muscle biopsies before, after 6 (short-), and 55 (long-term) days of bed rest. Glycogen and intramyocellular lipid deposits were assessed in electron microscopy images, and fasted blood glucose and insulin levels determined for the calculation of the HOMA-IR score.

Blood glucose remained constant throughout bed rest, but HOMA-IR scores were higher after short- and did not further change after long-term bed rest. Short-term bed rest did not cause significant changes in mitochondrial respiration, whilst long-term bed rest significantly reduced NADH- and oxidative phosphorylation capacity. Glycogen content and lipid droplets significantly increased after 6 days but only lipid droplets further accumulated after day 55. Metabolomics and lipidomics revealed reduced fatty acid oxidation and increased glucose metabolism after short-term bed rest, which manifested throughout the bed rest duration, suggestive of continuous alterations in skeletal muscle metabolism.

Short-term bed rest caused nutrient overload, a shift from fatty acid metabolism to glycolysis, and insulin insensitivity before a reduction in oxidative phosphorylation capacity was observed after long-term bed rest.

  1. Rudwill F, O'Gorman D, Lefai E, Chery I, Zahariev A, Normand S, Pagano AF, Chopard A, Damiot A, Laurens C, Hodson L, Canet-Soulas E, Heer M, Meuthen PF, Buehlmeier J, Baecker N, Meiller L, Gauquelin-Koch G, Blanc S, Simon C, Bergouignan A (2018) Metabolic inflexibility is an early marker of bed-rest–induced glucose intolerance even when fat mass is stable. https://doi.org/10.1210/jc.2017-02267
  2. Smith RL, Soeters MR, Wüst RCI, Houtkooper RH (2018) Metabolic flexibility as an adaptation to energy resources and requirements in health and disease. https://doi.org/10.1210/er.2017-00211
  3. Picard M, Jung B, Liang F, Azuelos I, Hussain S, Goldberg P, Godin R, Danialou G, Chaturvedi R, Rygiel K, Matecki S, Jaber S, Des Rosiers C, Karpati G, Ferri L, Burelle Y, Turnbull DM, Taivassalo T, Petrof BJ (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. https://doi.org/10.1164/rccm.201206-0982OC

Keywords: Bed rest, Skeletal muscle, Nutrient overload, Insulin resistance, Mitochondrial respiration Bioblast editor: Plangger M O2k-Network Lab: NL Amsterdam Wuest RC


Affiliations

Eggelbusch M1,2,3, Hendrickse P4, Schoonen R1, Giakoumaki I4, Kerkhoff TJ1, Grootemaat AE5, Rittweger J6, Ganse B4, Weeghel van M7, Mulder ER6, Degens H4, Wüst RCI1
  1. Lab for Myology, Dept of Human MVMT Sci, Fac of Behav and MVMT Sci, Vrije Univ Amsterdam, Amsterdam MVMT Sci
  2. Dept of Nutrition and Dietetics, Amsterdam UMC, Loc VUmc, Amsterdam MVMT Sciences
  3. Fac of Sports and Nutrition, Ctr of Expertise Urban Vitality, Amsterdam Univ of Appl Sci
  4. Manchester Metropolitan Univ, Res Ctr for MSK Sci & Sports Med, Fac of Sci and Engrg
  5. Electron Microsc Ctr Amsterdam, Dept of Med Biol, Acad Med Ctr
  6. Inst of Aerospace Med, German Aerospace Ctr (DLR)
  7. Amsterdam UMC, Univ of Amsterdam, Lab Genetic Metab Diseases, Amsterdam Cardiovasc Sci. -m.eggelbusch@amsterdamumc.nl

List of abbreviations, terms and definitions - MitoPedia

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Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Human  Tissue;cell: Skeletal muscle 



HRR: Oxygraph-2k  Event: B3