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Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Physical inactivity is a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). “Hybrid training”, a training that involves both voluntary and electrical muscle contractions, causes beneficial alterations in muscles even after short durations of exercise. The aim of this study was to investigate the therapeutic efficacy of hybrid training in patients with NAFLD.

Methods

Thirty-five patients with NAFLD who were resistant to lifestyle counseling were assigned to a hybrid-training group (n = 12) or a control group (n = 23). In the hybrid-training group, quadriceps and hamstrings were contracted voluntarily or electrically for 19 min twice a week. In the control group, patients received lifestyle counseling. The therapeutic efficacy of the hybrid training was evaluated after 12 weeks of the intervention.

Results

Serum alanine aminotransferase (ALT) levels and hepatic steatosis grade were significantly decreased in the hybrid-training group compared to that of the control group (−14.1 ± 5.8 vs. 3.5 ± 5.4 IU/mL; P < 0.05, −0.67 ± 0.19 vs. 0.09 ± 0.06 grade; P < 0.01, respectively). No significant changes were seen between the two groups in skeletal muscle mass. The decreases in homeostasis model assessment of insulin resistance (HOMA-IR) value and in serum IL-6 levels were significantly greater in the hybrid-training group than in the control group (−6.2 ± 3.2 vs. 0.4 ± 0.6; P < 0.05, −3.1 ± 1.1 vs. 1.1 ± 0.5 pg/mL; P < 0.01, respectively).

Conclusion

Hybrid training of voluntary and electrical muscle contractions improved hepatic steatosis and reduced insulin resistance and serum IL-6 levels in NAFLD patients who are resistant to lifestyle counseling.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

IL:

Interleukin

ALT:

Alanine aminotransferase

BIA:

Bioelectrical impedance analyzer

BMI:

Body mass index

CV:

Coefficient of variation

AST:

Aspartate aminotransferase

LDH:

Lactate dehydrogenase

ALP:

Alkaline phosphatase

GGT:

Gamma-glutamyl transpeptidase

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

BUN:

Blood urea nitrogen

CK:

Creatine kinase

HOMA-IR:

Homeostasis model assessment of insulin resistance

HOMA-%B:

Homeostasis model assessment of beta-cell function

EMS:

Electrical muscle stimulation

GLUT:

Glucose transporter

References

  1. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132:112–7.

    PubMed  CAS  Google Scholar 

  2. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–95.

    Article  PubMed  Google Scholar 

  3. Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology. 2008;134:1682–98.

    Article  PubMed  CAS  Google Scholar 

  4. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–21.

    Article  PubMed  Google Scholar 

  5. Loria P, Adinolfi LE, Bellentani S, Bugianesi E, Grieco A, Fargion S, et al. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis. 2010;42:272–82.

    Article  PubMed  CAS  Google Scholar 

  6. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49:608–12.

    Article  PubMed  Google Scholar 

  7. Soderberg C, Stal P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51:595–602.

    PubMed  Google Scholar 

  8. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51:679–89.

    Article  PubMed  CAS  Google Scholar 

  9. Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005;100:1072–81.

    Article  PubMed  Google Scholar 

  10. Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 2007;86:285–300.

    PubMed  CAS  Google Scholar 

  11. Devries MC, Samjoo IA, Hamadeh MJ, Tarnopolsky MA. Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women. Obesity (Silver Spring). 2008;16:2281–8.

    Article  CAS  Google Scholar 

  12. Shah K, Stufflebam A, Hilton TN, Sinacore DR, Klein S, Villareal DT. Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Obesity (Silver Spring). 2009;17:2162–8.

    Article  Google Scholar 

  13. Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol. 1997;27:103–7.

    Article  PubMed  CAS  Google Scholar 

  14. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology. 2009;49:306–17.

    Article  PubMed  Google Scholar 

  15. Terzis G, Georgiadis G, Stratakos G, Vogiatzis I, Kavouras S, Manta P, et al. Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects. Eur J Appl Physiol. 2008;102:145–52.

    Article  PubMed  CAS  Google Scholar 

  16. van Baak MA. Physical activity and energy balance. Public Health Nutr. 1999;2:335–9.

    PubMed  Google Scholar 

  17. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88:1379–406.

    Article  PubMed  CAS  Google Scholar 

  18. Bruun JM, Helge JW, Richelsen B, Stallknecht B. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am J Physiol Endocrinol Metab. 2006;290:E961–7.

    Article  PubMed  CAS  Google Scholar 

  19. van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008;48:449–57.

    Article  PubMed  Google Scholar 

  20. Frith J, Day CP, Robinson L, Elliott C, Jones DE, Newton JL. Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol. 2010;52:112–6.

    Article  PubMed  Google Scholar 

  21. Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004;53:413–9.

    Article  PubMed  CAS  Google Scholar 

  22. Suzuki A, Lindor K, St Saver J, Lymp J, Mendes F, Muto A, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol. 2005;43:1060–6.

    Article  PubMed  CAS  Google Scholar 

  23. Yanagi T, Shiba N, Maeda T, Iwasa K, Umezu Y, Tagawa Y, et al. Agonist contractions against electrically stimulated antagonists. Arch Phys Med Rehabil. 2003;84:843–8.

    Article  PubMed  Google Scholar 

  24. Yoshimitsu K, Shiba N, Matsuse H, Takano Y, Matsugaki T, Inada T, et al. Development of a training method for weightless environment using both electrical stimulation and voluntary muscle contraction. Tohoku J Exp Med. 2010;220:83–93.

    Article  PubMed  Google Scholar 

  25. Matsuse H, Shiba N, Umezu Y, Nago T, Maeda T, Tagawa Y, et al. Effects of a hybrid exercise on the activities of myogenic enzymes in plasma. Kurume Med J. 2006;53:47–51.

    Article  PubMed  CAS  Google Scholar 

  26. Iwasaki T, Shiba N, Matsuse H, Nago T, Umezu Y, Tagawa Y, et al. Improvement in knee extension strength through training by means of combined electrical stimulation and voluntary muscle contraction. Tohoku J Exp Med. 2006;209:33–40.

    Article  PubMed  Google Scholar 

  27. Nago T, Umezu Y, Shiba N, Matsuse H, Maeda T, Tagawa Y, et al. Muscle maintenance by volitional contraction against applied electrical stimulation. Kurume Med J. 2007;54:35–40.

    Article  PubMed  Google Scholar 

  28. Takano Y, Haneda Y, Maeda T, Sakai Y, Matsuse H, Kawaguchi T, et al. Increasing muscle strength and mass of thigh in elderly people with the hybrid-training method of electrical stimulation and volitional contraction. Tohoku J Exp Med. 2010;221:77–85.

    Article  PubMed  Google Scholar 

  29. Matsuse H, Shiba N, Umezu Y, Nago T, Tagawa Y, Kakuma T, et al. Muscle training by means of combined electrical stimulation and volitional contraction. Aviat Space Environ Med. 2006;77:581–5.

    PubMed  Google Scholar 

  30. American Gastroenterological Association. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology. 2002;123:1702–4.

    Article  Google Scholar 

  31. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    Article  PubMed  Google Scholar 

  32. Farrell GC, Chitturi S, Lau GK, Sollano JD. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol. 2007;22:775–7.

    Article  PubMed  Google Scholar 

  33. Oza N, Eguchi Y, Mizuta T, Ishibashi E, Kitajima Y, Horie H, et al. A pilot trial of body weight reduction for nonalcoholic fatty liver disease with a home-based lifestyle modification intervention delivered in collaboration with interdisciplinary medical staff. J Gastroenterol. 2009;44:1203–8.

    Article  PubMed  Google Scholar 

  34. Cunningham JJ. A reanalysis of the factors influencing basal metabolic rate in normal adults. Am J Clin Nutr. 1980;33:2372–4.

    PubMed  CAS  Google Scholar 

  35. Iwasa M, Hara N, Iwata K, Ishidome M, Sugimoto R, Tanaka H, et al. Restriction of calorie and iron intake results in reduction of visceral fat and serum alanine aminotransferase and ferritin levels in patients with chronic liver disease. Hepatol Res. 2010;40:1188–94.

    Article  PubMed  CAS  Google Scholar 

  36. Torimoto K, Hirayama A, Samma S, Yoshida K, Fujimoto K, Hirao Y. The relationship between nocturnal polyuria and the distribution of body fluid: assessment by bioelectric impedance analysis. J Urol. 2009;181:219–24. (discussion 24).

    Article  PubMed  Google Scholar 

  37. Sasaki N, Takeda S, Saito T, Ando Y, Kusano E. Analysis of metabolic syndrome and pulse wave velocity in hemodialysis patients: diagnosis of obesity by bioelectrical impedance analysis and a novel risk factor for atherosclerosis. Nippon Jinzo Gakkai Shi. 2009;51:476–83.

    PubMed  Google Scholar 

  38. Hara N, Iwasa M, Iwata K, Miyachi H, Tanaka H, Takeo M, et al. Value of the extracellular water ratio for assessment of cirrhotic patients with and without ascites. Hepatol Res. 2009;39:1072–9.

    Article  PubMed  CAS  Google Scholar 

  39. Kawaguchi T, Taniguchi E, Itou M, Ibi R, Okada T, Mutou M, et al. Body cell mass is a useful parameter for assessing malnutrition and severity of disease in non-ascitic cirrhotic patients with hepatocellular carcinoma or esophageal varices. Int J Mol Med. 2008;22:589–94.

    PubMed  CAS  Google Scholar 

  40. Heitmann BL. Impedance: a valid method in assessment of body composition? Eur J Clin Nutr. 1994;48:228–40.

    PubMed  CAS  Google Scholar 

  41. Kushner RF, Schoeller DA. Estimation of total body water by bioelectrical impedance analysis. Am J Clin Nutr. 1986;44:417–24.

    PubMed  CAS  Google Scholar 

  42. Kawaguchi T, Ide T, Taniguchi E, Hirano E, Itou M, Sumie S, et al. Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2. Am J Gastroenterol. 2007;102:570–6.

    Article  PubMed  Google Scholar 

  43. Kawaguchi T, Kuromatsu R, Ide T, Taniguchi E, Itou M, Sakata M, et al. Thrombocytopenia, an important interfering factor of antiviral therapy and hepatocellular carcinoma treatment for chronic liver diseases. Kurume Med J. 2009;56:9–15.

    Article  PubMed  CAS  Google Scholar 

  44. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol. 2004;165:1499–508.

    Article  PubMed  CAS  Google Scholar 

  45. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  PubMed  CAS  Google Scholar 

  46. Eguchi Y, Eguchi T, Mizuta T, Ide Y, Yasutake T, Iwakiri R, et al. Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease. J Gastroenterol. 2006;41:462–9.

    Article  PubMed  CAS  Google Scholar 

  47. Koda M, Kawakami M, Murawaki Y, Senda M. The impact of visceral fat in nonalcoholic fatty liver disease: cross-sectional and longitudinal studies. J Gastroenterol. 2007;42:897–903.

    Article  PubMed  Google Scholar 

  48. Sakurai M, Takamura T, Ota T, Ando H, Akahori H, Kaji K, et al. Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. J Gastroenterol. 2007;42:312–7.

    Article  PubMed  CAS  Google Scholar 

  49. Porcari JP, McLean KP, Foster C, Kernozek T, Crenshaw B, Swenson C. Effects of electrical muscle stimulation on body composition, muscle strength, and physical appearance. J Strength Cond Res. 2002;16:165–72.

    PubMed  Google Scholar 

  50. Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med. 2006;119:S10–6.

    Article  PubMed  Google Scholar 

  51. Klip A, Paquet MR. Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care. 1990;13:228–43.

    Article  PubMed  CAS  Google Scholar 

  52. Chilibeck PD, Bell G, Jeon J, Weiss CB, Murdoch G, MacLean I, et al. Functional electrical stimulation exercise increases GLUT-1 and GLUT-4 in paralyzed skeletal muscle. Metabolism. 1999;48:1409–13.

    Article  PubMed  CAS  Google Scholar 

  53. Lillioja S, Young AA, Culter CL, Ivy JL, Abbott WG, Zawadzki JK, et al. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest. 1987;80:415–24.

    Article  PubMed  CAS  Google Scholar 

  54. Oberbach A, Bossenz Y, Lehmann S, Niebauer J, Adams V, Paschke R, et al. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care. 2006;29:895–900.

    Article  PubMed  CAS  Google Scholar 

  55. Mohr T, Andersen JL, Biering-Sorensen F, Galbo H, Bangsbo J, Wagner A, et al. Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals. Spinal Cord. 1997;35:1–16.

    Article  PubMed  CAS  Google Scholar 

  56. Feve B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5:305–11.

    Article  PubMed  CAS  Google Scholar 

  57. Marra F, Bertolani C. Adipokines in liver diseases. Hepatology. 2009;50:957–69.

    Article  PubMed  CAS  Google Scholar 

  58. Kohut ML, McCann DA, Russell DW, Konopka DN, Cunnick JE, Franke WD, et al. Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun. 2006;20:201–9.

    Article  PubMed  CAS  Google Scholar 

  59. Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance. Diabetologia. 2003;46:1594–603.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported, in part, by a Grant-in-Aid for Young Scientists (B) (No. 22790874 to T.K.) and a Grant-in-Aid for Scientific Research (C) (No. 20500489 to Y.T. and No. 21590865 to M.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labour and Welfare of Japan, and by a Grant for Cancer Research from Fukuoka Cancer Society.

Conflict of interest

We have no financial relationships to disclose with regard to this study.

Author information

Authors and Affiliations

  1. Department of Digestive Disease Information and Research, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan

    Takumi Kawaguchi & Michio Sata

  2. Department of Medicine, Kurume University School of Medicine, Kurume, Japan

    Takumi Kawaguchi, Minoru Itou, Masahiro Sakata, Eitaro Taniguchi & Michio Sata

  3. Division of Rehabilitation, Kurume University Hospital, Kurume, Japan

    Naoto Shiba, Takashi Maeda & Yoshio Takano

  4. Department of Orthopedic Surgery, Kurume University School of Medicine, Kurume, 830-0011, Japan

    Toru Matsugaki & Kensei Nagata

  5. Department of Physical Therapy, Faculty of Medical Technology, Teikyo University Fukuoka, Omuta, 836-8505, Japan

    Yoshio Takano

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  1. Takumi Kawaguchi
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Correspondence to Takumi Kawaguchi.

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Kawaguchi, T., Shiba, N., Maeda, T. et al. Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study. J Gastroenterol 46, 746–757 (2011). https://doi.org/10.1007/s00535-011-0378-x

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