BACKGROUND & AIM: Dysfunction of skeletal muscle satellite cells might impair muscle regeneration and prolong ICU-acquired weakness, a condition associated with disability and delayed death. This study aimed to elucidate the distinct metabolic effects of critical illness and β-OH-butyrate on satellite cells isolated from these patients. METHODS: Satellite cells were extracted from vastus lateralis muscle biopsies of patients with ICU-acquired weakness (n = 10) and control group of healthy volunteers or patients undergoing elective hip replacement surgery (n = 10). The cells were exposed to standard culture media supplemented with β-OH-butyrate to assess its influence on cell proliferation by ELISA, mitochondrial functions by extracellular flux analysis, electron transport chain complexes by high resolution respirometry, and ROS production by confocal microscopy. RESULTS: Critical illness led to a decline in maximal respiratory capacity, ATP production and glycolytic capacity and increased ROS production in ICU patients' cells. Notably, the function of complex II was impaired due to critical illness but restored to normal levels upon exposure to β-OH-butyrate. While β-OH-butyrate significantly reduced ROS production in both control and ICU groups, it had no significant impact on global mitochondrial functions. CONCLUSION: Critical illness induces measurable bioenergetic dysfunction of skeletal muscle satellite cells. β-OH-butyrate displayed a potential in rectifying complex II dysfunction caused by critical illness and this warrants further exploration.

Department of Anaesthesia and Intensive Care of the 3rd Faculty of Medicine Královské Vinohrady University Hospital OXYLAB Laboratory for Mitochondrial Physiology Charles University Prague Czech Republic

Department of Internal Medicine of the 3rd Faculty of Medicine Královské Vinohrady University Hospital Charles University Prague Czech Republic; Department of Anaesthesia and Intensive Care of the 3rd Faculty of Medicine Královské Vinohrady University Hospital OXYLAB Laboratory for Mitochondrial Physiology Charles University Prague Czech Republic

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