Skip to main content
SpringerLink
Log in

Skeletal muscle mitochondrial mass is linked to lipid and metabolic profile in individuals with spinal cord injury

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ASIA:

American spinal injury association

BMR:

Basal metabolic rate

CIII:

Complex III

CS:

Citrate synthase

DXA:

Dual-energy X-ray absorptiometry

FFA:

Free fatty acids

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

LOI:

Level of injury

PGC-1α:

Peroxisome-proliferator-activated receptor-gamma co-activator 1alpha

SCI:

Spinal cord injury

S i :

Insulin sensitivity

S g :

Glucose effectiveness

TG:

Triglycerides

TSI:

Time since injury

VO2 peak:

Maximum oxygen uptake

References

  • Antoun G et al (2015) Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals. Diabetologia 58:2861–2866. doi:10.1007/s00125-015-3772-8

    Article  CAS  PubMed  Google Scholar 

  • Bauman WA, Spungen AM (1994) Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia: a model of premature aging. Metabolism 43:749–756

    Article  CAS  PubMed  Google Scholar 

  • Bauman WA, Spungen AM (2001) Carbohydrate and lipid metabolism in chronic spinal cord injury. J Spinal Cord Med 24:266–277

    Article  CAS  PubMed  Google Scholar 

  • Bauman WA, Spungen AM, Zhong YG, Rothstein JL, Petry C, Gordon SK (1992) Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury. Paraplegia 30:697–703. doi:10.1038/sc.1992.136

    CAS  PubMed  Google Scholar 

  • Bharadwaj MS, Tyrrell DJ, Lyles MF, Demons JL, Rogers GW, Molina AJ (2015) Preparation and respirometric assessment of mitochondria isolated from skeletal muscle tissue obtained by percutaneous needle biopsy. J Vis Exp. doi:10.3791/52350

    PubMed  PubMed Central  Google Scholar 

  • Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN (2003) MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 5:1003–1015. doi:10.1089/152091503322641060

    Article  CAS  PubMed  Google Scholar 

  • Brass EP, Hiatt WR, Gardner AW, Hoppel CL (2001) Decreased NADH dehydrogenase and ubiquinol-cytochrome c oxidoreductase in peripheral arterial disease. Am J Physiol Heart Circ Physiol 280:H603–H609

    CAS  PubMed  Google Scholar 

  • Brown MS, Goldstein JL (1984) How LDL receptors influence cholesterol and atherosclerosis. Sci Am 251:58–66

    Article  CAS  PubMed  Google Scholar 

  • Buchholz AC, McGillivray CF, Pencharz PB (2003) Differences in resting metabolic rate between paraplegic and able-bodied subjects are explained by differences in body composition. Am J Clin Nutr 77:371–378

    CAS  PubMed  Google Scholar 

  • Carter HN, Chen CC, Hood DA (2015) Mitochondria, muscle health, and exercise with advancing age. Physiology (Bethesda) 30:208–223. doi:10.1152/physiol.00039.2014

    CAS  Google Scholar 

  • Castro MJ, Apple DF Jr, Staron RS, Campos GE, Dudley GA (1999) Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury. J Appl Physiol (1985) 86:350–358

    CAS  Google Scholar 

  • Chilibeck PD et al (1999) Functional electrical stimulation exercise increases GLUT-1 and GLUT-4 in paralyzed skeletal muscle. Metabolism 48:1409–1413

    Article  CAS  PubMed  Google Scholar 

  • Chomentowski P, Coen PM, Radikova Z, Goodpaster BH, Toledo FG (2011) Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. J Clin Endocrinol Metab 96:494–503. doi:10.1210/jc.2010-0822

    Article  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP (1981) The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30:1000–1007

    Article  CAS  PubMed  Google Scholar 

  • Distefano G et al (2016) Chronological age does not influence ex-vivo mitochondrial respiration and quality control in skeletal muscle. J Gerontol A Biol Sci Med Sci. doi:10.1093/gerona/glw102

    Google Scholar 

  • Duckworth WC, Solomon SS, Jallepalli P, Heckemeyer C, Finnern J, Powers A (1980) Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Diabetes 29:906–910

    Article  CAS  PubMed  Google Scholar 

  • Essén B, Jansson E, Henriksson J, Taylor AW, Saltin B (1975) Metabolic characteristics of fibre types in human skeletal muscle. Acta Physiol Scand 95(2):153–165

    Article  PubMed  Google Scholar 

  • Essén-Gustavsson B, Henriksson J (1984) Enzyme levels in pools of microdissected human muscle fibers of identified type. Adaptive response to exercise. Acta Physiol Scand 120(4):505–515

    Article  PubMed  Google Scholar 

  • Gorgey AS, Dudley GA (2007) Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury. Spinal Cord 45:304–309. doi:10.1038/sj.sc.3101968

    Article  CAS  PubMed  Google Scholar 

  • Gorgey AS, Gater DR (2011) Regional and relative adiposity patterns in relation to carbohydrate and lipid metabolism in men with spinal cord injury. Appl Physiol Nutr Metab 36(1):107–114

    Article  CAS  PubMed  Google Scholar 

  • Gorgey AS, Lawrence J (2016) Acute responses of functional electrical stimulation cycling on the ventilation-to-CO2 production ratio and substrate utilization after spinal cord injury. PMR 8(3):225–234

    Article  Google Scholar 

  • Gorgey AS, Chiodo AE, Zemper ED, Hornyak JE, Rodriguez GM, Gater DR (2010) Relationship of spasticity to soft tissue body composition and the metabolic profile in persons with chronic motor complete spinal cord injury. J Spinal Cord Med 33:6–15

    Article  PubMed  PubMed Central  Google Scholar 

  • Gorgey AS, Harnish CR, Daniels JA, Dolbow DR, Keeley A, Moore J, Gater DR (2012) A report of anticipated benefits of functional electrical stimulation after spinal cord injury. J Spinal Cord Med 35:107–112. doi:10.1179/204577212X13309481546619

    Article  PubMed  PubMed Central  Google Scholar 

  • Gorgey AS, Poarch HJ, Dolbow DD, Castillo T, Gater DR (2014) Effect of adjusting pulse durations of functional electrical stimulation cycling on energy expenditure and fatigue after spinal cord injury. J Rehabil Res Dev 51:1455–1468. doi:10.1682/JRRD.2014.02.0054

    Article  PubMed  Google Scholar 

  • Gorgey AS, Khalil RE, Gill R, O’Brien LC, Lais T, Castillo T, Cifu DX, Savas J, Khan R, Cardozo C, Lesnefsky EJ, Gater DR, Adler RA (2017) Effects of testosterone and evoked resistance exercise after spinal cord injury (TEREX-SCI): study protocol for a randomized controlled trial. BMJ Open 7:e014125. doi:10.1136/bmjopen-2016-014125

    Article  PubMed  PubMed Central  Google Scholar 

  • Grimby G, Broberg C, Krotkiewska I, Krotkiewski M (1976) Muscle fiber composition in patients with traumatic cord lesion. Scand J Rehabil Med 8:37–42

    CAS  PubMed  Google Scholar 

  • Hesselink MK, Schrauwen-Hinderling V, Schrauwen P (2016) Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus. Nat Rev Endocrinol 12:633–645. doi:10.1038/nrendo.2016.104

    Article  CAS  PubMed  Google Scholar 

  • Hutchison SK, Teede HJ, Rachon D, Harrison CL, Strauss BJ, Stepto NK (2012) Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome. Diabetologia 55:1424–1434. doi:10.1007/s00125-011-2442-8

    Article  CAS  PubMed  Google Scholar 

  • Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950

    Article  CAS  PubMed  Google Scholar 

  • Kirkwood SP, Zurlo F, Larson K, Ravussin E (1991) Muscle mitochondrial morphology, body composition, and energy expenditure in sedentary individuals. Am J Physiol 260:E89–E94

    CAS  PubMed  Google Scholar 

  • Kjaer M, Mohr T, Biering-Sorensen F, Bangsbo J (2001) Muscle enzyme adaptation to training and tapering-off in spinal-cord-injured humans. Eur J Appl Physiol 84:482–486

    Article  CAS  PubMed  Google Scholar 

  • Koves TR et al (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7:45–56. doi:10.1016/j.cmet.2007.10.013

    Article  CAS  PubMed  Google Scholar 

  • Kramer DK, Ahlsen M, Norrbom J, Jansson E, Hjeltnes N, Gustafsson T, Krook A (2006) Human skeletal muscle fibre type variations correlate with PPAR alpha, PPAR delta and PGC-1 alpha mRNA. Acta Physiol (Oxf) 188:207–216. doi:10.1111/j.1748-1716.2006.01620.x

    Article  CAS  Google Scholar 

  • Lalia AZ et al (2016) Predictors of whole-body insulin sensitivity across ages and adiposity in adult humans. J Clin Endocrinol Metab 101:626–634. doi:10.1210/jc.2015-2892

    Article  PubMed  Google Scholar 

  • Magnusson G, Kaijser L, Rong H, Isberg B, Sylven C, Saltin B (1996) Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle. Clin Physiol 16:183–195

    Article  CAS  PubMed  Google Scholar 

  • Maki KC, Briones ER, Langbein WE, Inman-Felton A, Nemchausky B, Welch M, Burton J (1995) Associations between serum lipids and indicators of adiposity in men with spinal cord injury. Paraplegia 33:102–109. doi:10.1038/sc.1995.24

    CAS  PubMed  Google Scholar 

  • Mogensen M, Sahlin K, Fernstrom M, Glintborg D, Vind BF, Beck-Nielsen H, Hojlund K (2007) Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56:1592–1599. doi:10.2337/db06-0981

    Article  CAS  PubMed  Google Scholar 

  • Nash MS, Mendez AJ (2007) A guideline-driven assessment of need for cardiovascular disease risk intervention in persons with chronic paraplegia. Arch Phys Med Rehabil 88:751–757. doi:10.1016/j.apmr.2007.02.031

    Article  PubMed  Google Scholar 

  • O’Brien LC, Wade RC, Segal L, Chen Q, Savas J, Lesnefsky EJ, Gorgey AS (2017) Mitochondrial mass and activity as a function of body composition in individuals with spinal cord injury. Physiol Rep. doi:10.14814/phy2.13080

    PubMed  PubMed Central  Google Scholar 

  • Ravussin E, Bogardus C (1992) A brief overview of human energy metabolism and its relationship to essential obesity. Am J Clin Nutr 55:242S–245S

    CAS  PubMed  Google Scholar 

  • Reaven GM, Chen N, Hollenbeck C, Chen YD (1989) Effect of age on glucose tolerance and glucose uptake in healthy individuals. J Am Geriatr Soc 37:735–740

    Article  CAS  PubMed  Google Scholar 

  • Ryan TE, Brizendine JT, Backus D, McCully KK (2013) Electrically induced resistance training in individuals with motor complete spinal cord injury. Arch Phys Med Rehabil 94:2166–2173. doi:10.1016/j.apmr.2013.06.016

    Article  PubMed  Google Scholar 

  • Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: unravelling the mechanism. Lancet 375:2267–2277. doi:10.1016/S0140-6736(10)60408-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrauwen-Hinderling VB et al (2007) Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects. Diabetologia 50:113–120. doi:10.1007/s00125-006-0475-1

    Article  CAS  PubMed  Google Scholar 

  • Selsby JT, Morine KJ, Pendrak K, Barton ER, Sweeney HL (2012) Rescue of dystrophic skeletal muscle by PGC-1alpha involves a fast to slow fiber type shift in the mdx mouse. PLoS One 7:e30063. doi:10.1371/journal.pone.0030063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spungen AM, Adkins RH, Stewart CA, Wang J, Pierson RN Jr, Waters RL, Bauman WA (2003) Factors influencing body composition in persons with spinal cord injury: a cross-sectional study. J Appl Physiol (1985) 95:2398–2407. doi:10.1152/japplphysiol.00729.2002

    Article  Google Scholar 

  • St-Jean-Pelletier F et al (2016) The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men. J Cachexia Sarcopenia Muscle. doi:10.1002/jcsm.12139

    PubMed  PubMed Central  Google Scholar 

  • Talayero BG, Sacks FM (2011) The role of triglycerides in atherosclerosis. Curr Cardiol Rep 13:544–552. doi:10.1007/s11886-011-0220-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Toth PP (2005) Cardiology patient page. The “good cholesterol”: high-density lipoprotein. Circulation 111:e89–e91. doi:10.1161/01.CIR.0000154555.07002.CA

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the Hunter Holmes McGuire Medical Center for allowing the opportunity to conduct clinical research and all of our participants. Thanks to Refka Khalil for research coordination and to Jeremy Thompson and Ying Hu for technical assistance.

Author information

Authors and Affiliations

  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

    Laura C. O’Brien & Ashraf S. Gorgey

  2. Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, USA

    Laura C. O’Brien & Edward J. Lesnefsky

  3. Division of Cardiology, Department of Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA

    Qun Chen & Edward J. Lesnefsky

  4. Surgery, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Jeannie Savas

  5. Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA

    Jeannie Savas

  6. Medical Services, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA

    Edward J. Lesnefsky

  7. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA

    Edward J. Lesnefsky

  8. Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA

    Ashraf S. Gorgey

Authors
  1. Laura C. O’Brien
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeannie Savas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edward J. Lesnefsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ashraf S. Gorgey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashraf S. Gorgey.

Ethics declarations

Grants

This work was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs Grant # B7867-W.

Conflict of interest

The authors declare no conflict of interest.

Additional information

Communicated by William J. Kraemer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

O’Brien, L.C., Chen, Q., Savas, J. et al. Skeletal muscle mitochondrial mass is linked to lipid and metabolic profile in individuals with spinal cord injury. Eur J Appl Physiol 117, 2137–2147 (2017). https://doi.org/10.1007/s00421-017-3687-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-017-3687-9

Keywords

Search

Navigation