Laura C O'Brien1,2, Qun Chen3, Jeannie Savas4,5, Edward J Lesnefsky2,3,6,7, Ashraf S Gorgey8,9. 1. Spinal Cord Injury Research, Spinal Cord Injury and Disorders Service, Hunter Holmes McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA, 23249, USA. 2. Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, USA. 3. Division of Cardiology, Department of Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA. 4. Surgery, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA. 5. Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA. 6. Medical Services, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA. 7. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA. 8. Spinal Cord Injury Research, Spinal Cord Injury and Disorders Service, Hunter Holmes McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA, 23249, USA. ashraf.gorgey@va.gov. 9. Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA. ashraf.gorgey@va.gov.
Abstract
PURPOSE: Changes in metabolism and body composition after spinal cord injury (SCI) predispose individuals to obesity, type II diabetes, and cardiovascular disease. A link between lean mass and skeletal muscle mitochondrial mass has been reported but it is unknown how skeletal muscle mitochondrial mass and activity impact metabolic health. This study examined the relationship between skeletal muscle mitochondrial mass, activity and metabolic profile in individuals with chronic SCI. METHODS: Twenty-two men with motor complete SCI participated in the study. Citrate synthase (CS) and complex III (CIII) activity was measured in vastus lateralis biopsies. Metabolic profile was assessed by intravenous glucose tolerance test, basal metabolic rate (BMR), maximum oxygen uptake (VO2 peak) and blood lipid profile. RESULTS: Skeletal muscle CS activity was negatively related to the cholesterol:high density lipoprotein cholesterol (HDL-C) ratio and triglycerides (r = -0.60, p = 0.009; r = -0.64, p = 0.004, respectively). CS activity was positively related to insulin sensitivity and BMR (r = 0.67, p = 0.006; r = 0.64, p = 0.005, respectively). Similar relationships were found for CIII and metabolic profile, but not CIII normalized to CS. Many of the relationships between CS and metabolism remained significant when age, level of injury, or time since injury were accounted for. They also remained significant when CS activity was normalized to total lean mass. CONCLUSIONS: These results suggest that an increase in skeletal muscle mitochondrial mass is associated with improved metabolic health independent of age, level of injury, or time since injury in individuals with chronic SCI. This highlights the importance of maintaining and improving mitochondrial health in individuals with SCI.
PURPOSE: Changes in metabolism and body composition after spinal cord injury (SCI) predispose individuals to obesity, type II diabetes, and cardiovascular disease. A link between lean mass and skeletal muscle mitochondrial mass has been reported but it is unknown how skeletal muscle mitochondrial mass and activity impact metabolic health. This study examined the relationship between skeletal muscle mitochondrial mass, activity and metabolic profile in individuals with chronic SCI. METHODS: Twenty-two men with motor complete SCI participated in the study. Citrate synthase (CS) and complex III (CIII) activity was measured in vastus lateralis biopsies. Metabolic profile was assessed by intravenous glucose tolerance test, basal metabolic rate (BMR), maximum oxygen uptake (VO2 peak) and blood lipid profile. RESULTS: Skeletal muscle CS activity was negatively related to the cholesterol:high density lipoprotein cholesterol (HDL-C) ratio and triglycerides (r = -0.60, p = 0.009; r = -0.64, p = 0.004, respectively). CS activity was positively related to insulin sensitivity and BMR (r = 0.67, p = 0.006; r = 0.64, p = 0.005, respectively). Similar relationships were found for CIII and metabolic profile, but not CIII normalized to CS. Many of the relationships between CS and metabolism remained significant when age, level of injury, or time since injury were accounted for. They also remained significant when CS activity was normalized to total lean mass. CONCLUSIONS: These results suggest that an increase in skeletal muscle mitochondrial mass is associated with improved metabolic health independent of age, level of injury, or time since injury in individuals with chronic SCI. This highlights the importance of maintaining and improving mitochondrial health in individuals with SCI.
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