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Author Spotlight: Unveiling Mitochondrial Function and Cellular Metabolic Adaptation in Metabolic Diseases
Published on: October 4, 2024
Skeletal Muscle Mitochondrial Function is Determined by Burn Severity, Sex, and Sepsis, and is Associated With
Victoria G Rontoyanni1,2, Ioannis Malagaris1,3, David N Herndon1,2,4
1Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas.
Insights
Severe burn injuries impact skeletal muscle mitochondrial function in children, with burn size, sex, and sepsis playing key roles. Restoring mitochondrial function may improve glucose control and functional capacity in burn survivors.
Area of Science:
- Biochemistry
- Physiology
- Pediatric Medicine
Background:
- Restoring normal mitochondrial function is a novel therapeutic target for mitigating stress responses and improving recovery from severe burn trauma.
- Understanding the factors influencing skeletal muscle mitochondrial function in burned children is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the determinants of skeletal muscle mitochondrial respiratory capacity and function in children who have experienced severe burns.
- To assess the association between mitochondrial function, glucose metabolism, and functional capacity (VO2peak) in this patient population.
Main Methods:
- Analysis of data from burned children in the placebo arm of a prospective clinical trial.
- Determination of mitochondrial respiratory capacity using high-resolution respirometry in permeabilized myofibers.
- Assessment of glucose kinetics and cardiorespiratory fitness (VO2peak) in subsets of participants.
- Application of mixed multiple regression models to identify determinants and associations.
Main Results:
- Increasing burn size correlated with greater ATP-producing respiration.
- Girls exhibited significantly lower coupled respiration and respiratory control compared to boys.
- Sepsis was associated with reduced coupled respiration.
- Hepatic glucose release was linked to enhanced coupled respiration and respiratory control.
- Coupled respiration showed a positive association with VO2peak.
Conclusions:
- Skeletal muscle mitochondrial function in burned children is significantly influenced by burn severity, sex, and the presence of sepsis.
- Altered mitochondrial respiratory function in burn survivors is associated with impaired glucose control and reduced functional capacity.
- These findings underscore the critical role of muscle bioenergetics in the clinical outcomes of severe burn trauma.
Background:
Restoring normal mitochondrial function represents a new target for strategies aimed at mitigating the stress response to severe burn trauma and hastening recovery. Our objective was to investigate the determinants of skeletal muscle mitochondrial respiratory capacity and function and its association with glucose metabolism and functional capacity in burned children.
Methods:
Data from burned children enrolled in the placebo arm of an ongoing prospective clinical trial were analyzed. Mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry on at least one occasion per participant. In subsets of patients, glucose kinetics and cardiorespiratory fitness (VO2peak) were also determined. Mixed multiple regression models were used to identify the determinants of mitochondrial respiratory function and to assess the relationship between mitochondrial respiration and both glucose control and functional capacity (VO2peak).
Main Results:
Increasing full-thickness burn size was associated with greater adjusted coupled (ATP-producing) respiration, adjusted for age, sex, sepsis, and time of testing (P < 0.01; n = 55, obs = 97). Girls had on average 23.3% lower coupled respiration (adjusted mean and 95% confidence of interval [CI], -7.1; -12.6 to -1.7 pmol/s/mg; P < 0.025) and 29.8% lower respiratory control than boys (adjusted mean and 95% CI, -0.66; -1.07 to -0.25; P < 0.01; n = 55, obs = 97). The presence of sepsis was associated with lower respiration coupled to ATP production by an average of 25.5% compared with nonsepsis (adjusted mean and 95% CI, -6.9; -13.0 to -0.7 pmol/s/mg; P < 0.05; n = 55, obs = 97), after adjustment for age, sex, full-thickness burn size, and time of testing. During a hyperinsulinemic euglycemic clamp, hepatic glucose release was associated with greater coupled respiration and respiratory control (P < 0.05; n = 42, obs = 73), independent of age, sepsis, full-thickness burn size, and time postinjury testing. Coupled respiration was positively associated with VO2peak after adjustment for age, full-thickness burn size, and time of exercise testing (P < 0.025; n = 18, obs = 25).
Conclusions:
Burn severity, sex, and sepsis influence skeletal muscle mitochondrial function in burned children. Glucose control and functional capacity are associated with altered mitochondrial respiratory function in muscle of burn survivors, highlighting the relationship of altered muscle bioenergetics with the clinical sequelae accompanying severe burn trauma.
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