Obesity Surgery

, Volume 26, Issue 7, pp 1391–1397 | Cite as

Improved Muscle Mitochondrial Capacity Following Gastric Bypass Surgery in Obese Subjects

  • Maria Fernström
  • Linda Bakkman
  • Peter Loogna
  • Olav Rooyackers
  • Madeleine Svensson
  • Towe Jakobsson
  • Lena Brandt
  • Ylva Trolle LagerrosEmail author
Original Contributions



Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance.


Eleven women with a median BMI of 38.5 kg/m2 (q-range 37–40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio).


At follow-up, the participants had a median BMI of 29.6 kg/m2 (28.3–32.0). State 3 increased from 20.6 (17.9–28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0–49.0), p = 0.01, while state 4 increased from 2.8 (1.8–4.2) to 4.2 nmol O2/min/U CS (3.1–6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5–2.8) to 3.2 (3.0–3.4), p = 0.02, indicating improved mitochondrial efficiency.


Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.


Energy metabolism Mitochondria Muscle Obesity Thermogenesis Weight loss 



The authors would like to acknowledge Susanne Rantakyrö at the Bariatric Center for outstanding coordination of the biopsy and blood sampling. Finally, we greatly appreciate the research volunteers who participated in the study.

Compliance with Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and later amendments or comparable ethical standards. The study was approved by the ethics committee of Karolinska Institutet, Stockholm, Sweden.

Grant Information

Financial support was provided through grants from the Swedish Transport Administration, the Swedish Nutrition Foundation, the Swedish Research Council (no: 14244), Stiftelsen Serafimerlasarettet, and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet. The pedometers were generously provided by Abbott Scandinavia AB.

Conflict of Interest

Maria Fernström, Linda Bakkman, Peter Loogna, Olav Rooyackers, Madeleine Svensson, Towe Jakobsson, and Lena Brandt declare that they have no conflict of interest. Ylva Trolle Lagerros reports receiving consulting fees from Novo Nordisk.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Mitchell NS, Catenacci VA, Wyatt HR, et al. Obesity: overview of an epidemic. Psychiatr Clin N Am. 2011;34(4):717–32. PubMed Pubmed Central PMCID: 3228640.CrossRefGoogle Scholar
  2. 2.
    Christiansen E, Garby L. Prediction of body weight changes caused by changes in energy balance. Eur J Clin Invest. 2002;32(11):826–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Avenell A, Broom J, Brown TJ, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess. 2004;8(21):1–182.CrossRefGoogle Scholar
  4. 4.
    Heymsfield SB, Harp JB, Reitman ML, et al. Why do obese patients not lose more weight when treated with low-calorie diets? A mechanistic perspective. Am J Clin Nutr. 2007;85(2):346–54.PubMedGoogle Scholar
  5. 5.
    Major GC, Doucet E, Trayhurn P, et al. Clinical significance of adaptive thermogenesis. Int J Obes (Lond). 2007;31(2):204–12.CrossRefGoogle Scholar
  6. 6.
    Wamsteker EW, Geenen R, Zelissen PM, et al. Unrealistic weight-loss goals among obese patients are associated with age and causal attributions. J Am Diet Assoc. 2009;109(11):1903–8. PubMed.CrossRefPubMedGoogle Scholar
  7. 7.
    Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005;82(1 Suppl):222S–5.PubMedGoogle Scholar
  8. 8.
    Dulloo AG, Jacquet J. Adaptive reduction in basal metabolic rate in response to food deprivation in humans: a role for feedback signals from fat stores. Am J Clin Nutr. 1998;68(3):599–606.PubMedGoogle Scholar
  9. 9.
    Prentice AM, Goldberg GR, Jebb SA, et al. Physiological responses to slimming. Proc Nutr Soc. 1991;50(2):441–58.CrossRefPubMedGoogle Scholar
  10. 10.
    Rosenbaum M, Hirsch J, Gallagher DA, et al. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. 2008;88(4):906–12.PubMedGoogle Scholar
  11. 11.
    Bakkman L, Fernstrom M, Loogna P, et al. Reduced respiratory capacity in muscle mitochondria of obese subjects. Obes Facts. 2010;3(6):371–5. PubMed.PubMedGoogle Scholar
  12. 12.
    Rolfe DF, Brand MD. Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate. Am J Physiol. 1996;271(4 Pt 1):C1380–9. PubMed.PubMedGoogle Scholar
  13. 13.
    Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Investig. 1975;35(7):609–16. PubMed.CrossRefGoogle Scholar
  14. 14.
    Tonkonogi M, Walsh B, Tiivel T, et al. Mitochondrial function in human skeletal muscle is not impaired by high intensity exercise. Pflugers Arch. 1999;437(4):562–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem. 1955;217(1):383–93. PubMed.PubMedGoogle Scholar
  16. 16.
    Chambers AP, Jessen L, Ryan KK, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology. 2011;141(3):950–8. PubMed Pubmed Central PMCID: 3163814.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Liou AP, Paziuk M, Luevano Jr JM, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra41.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ahmad NN, Pfalzer A, Kaplan LM. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes. 2013;37(12):1553–9.CrossRefGoogle Scholar
  19. 19.
    Houmard JA, Tanner CJ, Yu C, et al. Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects. Diabetes. 2002;51(10):2959–63.CrossRefPubMedGoogle Scholar
  20. 20.
    Coen PM, Goodpaster BH. Role of intramyocellular lipids in human health. Trends Endocrinol Metab. 2012;23(8):391–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Hempenstall S, Page MM, Wallen KR, et al. Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice. Mech Ageing Dev. 2012;133(1):37–45.CrossRefPubMedGoogle Scholar
  22. 22.
    Thrush AB, Dent R, McPherson R, et al. Implications of mitochondrial uncoupling in skeletal muscle in the development and treatment of obesity. FEBS J. 2013;280(20):5015–29. PubMed.CrossRefPubMedGoogle Scholar
  23. 23.
    Vijgen GH, Bouvy ND, Hoeks J, et al. Impaired skeletal muscle mitochondrial function in morbidly obese patients is normalized one year after bariatric surgery. Surg Obes Relat Dis. 2013;9(6):936–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Nijhawan S, Richards W, O’Hea MF, et al. Bariatric surgery rapidly improves mitochondrial respiration in morbidly obese patients. Surg Endosc. 2013;27(12):4569–73. PubMed.CrossRefPubMedGoogle Scholar
  25. 25.
    Wijers SL, Saris WH, van Marken Lichtenbelt WD. Recent advances in adaptive thermogenesis: potential implications for the treatment of obesity. Obes Rev. 2009;10(2):218–26.CrossRefPubMedGoogle Scholar
  26. 26.
    van den Berg SA, van Lichtenbelt Marken W, Willems van Dijk K, et al. Skeletal muscle mitochondrial uncoupling, adaptive thermogenesis and energy expenditure. Curr Opin Clin Nutr Metab Care. 2011;14(3):243–9. PubMed.CrossRefPubMedGoogle Scholar
  27. 27.
    Cannon B, Nedergaard J. Thermogenesis challenges the adipostat hypothesis for body-weight control. Proc Nutr Soc. 2009;68(4):401–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Fisher-Wellman KH, Weber TM, Cathey BL, et al. Mitochondrial respiratory capacity and content are normal in young insulin-resistant obese humans. Diabetes. 2014;63(1):132–41. PubMed Pubmed Central PMCID: 3868052.CrossRefPubMedGoogle Scholar
  29. 29.
    Boushel R, Gnaiger E, Schjerling P, et al. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia. 2007;50(4):790–6. PubMed Pubmed Central PMCID: 1820754.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ritov VB, Menshikova EV, Azuma K, et al. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab. 2010;298(1):E49–58. PubMed Pubmed Central PMCID: 2806111.CrossRefPubMedGoogle Scholar
  31. 31.
    Picard M, Taivassalo T, Ritchie D, et al. Mitochondrial structure and function are disrupted by standard isolation methods. PLoS One. 2011;6(3):e18317.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rabol R, Svendsen PF, Skovbro M, et al. Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. Metabolism. 2009;58(8):1145–52.CrossRefPubMedGoogle Scholar
  33. 33.
    Figueiredo PA, Ferreira RM, Appell HJ, et al. Age-induced morphological, biochemical, and functional alterations in isolated mitochondria from murine skeletal muscle. J Gerontol Series A Biol Sci Med Sci. 2008;63(4):350–9. PubMed.CrossRefGoogle Scholar
  34. 34.
    Boyle KE, Zheng D, Anderson EJ, Neufer PD, Houmard JA. Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans. Int J Obes (Lond). 2011 Oct 25. PubMed Epub 2011/10/26. Eng.Google Scholar
  35. 35.
    Menshikova EV, Ritov VB, Toledo FG, et al. Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity. Am J Physiol Endocrinol Metab. 2004;288(4):E818–25.CrossRefPubMedGoogle Scholar
  36. 36.
    le Roux CW, Bueter M, Theis N, et al. Gastric bypass reduces fat intake and preference. Am J Physiol Regul, Integr Comp Physiol. 2011;301(4):R1057–66. PubMed Pubmed Central PMCID: 3197335.CrossRefGoogle Scholar
  37. 37.
    Olbers T, Bjorkman S, Lindroos A, et al. Body composition, dietary intake, and energy expenditure after laparoscopic Roux-en-Y gastric bypass and laparoscopic vertical banded gastroplasty: a randomized clinical trial. Ann Surg. 2006;244(5):715–22.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Bevilacqua L, Ramsey JJ, Hagopian K, et al. Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production. Am J Physiol Endocrinol Metab. 2004;286(5):E852–61.CrossRefPubMedGoogle Scholar
  39. 39.
    Lal SB, Ramsey JJ, Monemdjou S, et al. Effects of caloric restriction on skeletal muscle mitochondrial proton leak in aging rats. J Gerontol A Biol Sci Med Sci. 2001;56(3):B116–22.CrossRefPubMedGoogle Scholar
  40. 40.
    Harper ME, Dent R, Monemdjou S, et al. Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women. Diabetes. 2002;51(8):2459–66.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Maria Fernström
    • 1
  • Linda Bakkman
    • 2
  • Peter Loogna
    • 3
  • Olav Rooyackers
    • 4
  • Madeleine Svensson
    • 2
    • 5
  • Towe Jakobsson
    • 4
  • Lena Brandt
    • 1
  • Ylva Trolle Lagerros
    • 2
    • 6
    Email author
  1. 1.Department of Clinical Medicine, School of Health and Medical SciencesÖrebro UniversityÖrebroSweden
  2. 2.Department of Medicine, Clinical Epidemiology UnitKarolinska Institutet SolnaStockholmSweden
  3. 3.Bariatric CenterSophiahemmetStockholmSweden
  4. 4.Department of Anaesthesiology and Intensive CareKarolinska Institutet HuddingeStockholmSweden
  5. 5.School of Health and Social SciencesHalmstad UniversityHalmstadSweden
  6. 6.Department of Endocrinology, Metabolism and DiabetesKarolinska University Hospital HuddingeStockholmSweden

Personalised recommendations