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Skeletal muscle mass to visceral fat area ratio is an important determinant affecting hepatic conditions of non-alcoholic fatty liver disease

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

Abstract

Background

Not only obesity but also sarcopenia is associated with NAFLD. The influence of altered body composition on the pathophysiology of NAFLD has not been fully elucidated. The aim of this study is to determine whether skeletal muscle mass to visceral fat area ratio (SV ratio) affects NAFLD pathophysiology.

Methods

A total of 472 subjects were enrolled. The association between SV ratio and NAFLD pathophysiological factors was assessed in a cross-sectional nature by stratification analysis.

Results

When the SV ratio was stratified by quartiles (Q 1–Q 4), the SV ratio showed a negative relationship with the degree of body mass index, HOMA-IR, and liver stiffness (Q 1, 8.9 ± 7.5 kPa, mean ± standard deviation; Q 2, 7.5 ± 6.2; Q 3, 5.8 ± 3.7; Q 4, 5.0 ± 1.9) and steatosis (Q 1, 282 ± 57 dB/m; Q 2, 278 ± 58; Q 3, 253 ± 57; Q 4, 200 ± 42) measured by transient elastography. Levels of leptin and biochemical markers of liver cell damage, liver fibrosis, inflammation and oxidative stress, and hepatocyte apoptosis were significantly higher in subjects in Q 1 than in those in Q 2, Q 3, or Q 4. Moreover, fat contents in femoral muscles were significantly higher in subjects in Q 1 and the change was associated with weakened muscle strength. In logistic regression analysis, NAFLD subjects with the decreased SV ratio were likely to have an increased risk of moderate-to-severe steatosis and that of advanced fibrosis.

Conclusions

Decreased muscle mass coupled with increased visceral fat mass is closely associated with an increased risk for exacerbating NAFLD pathophysiology.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BMI:

Body mass index

CAP:

Controlled attenuation parameter

CEUS:

Contrast-enhanced ultrasonography

EMCL:

Extra-myocellular lipid

FFA:

Free fatty acid

FGF21:

Fibroblast growth factor 21

FPG:

Fasting plasma glucose

HDL-C:

High-density lipoprotein-cholesterol

HOMA-IR:

Homeostasis model assessment-insulin resistance

hs-CRP:

High-sensitivity C-reactive protein

IHL:

Intrahepatic lipid

IL-6:

Interleukin-6

IMCL:

Intra-myocellular lipid

LDL-C:

Low-density lipoprotein-cholesterol

LPS:

Lipopolysaccharide

LS:

Liver stiffness

1H-MRS:

Proton magnetic resonance spectroscopy

MSTN:

Myostatin

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

Sep:

Selenoprotein-P

SV ratio:

Skeletal muscle mass to visceral fat area ratio

TBARS:

2-Thiobarbituric acid reactive substances

TG:

Triglyceride

TNF-α:

Tumor necrosis factor-α

γ-GT:

gamma-Glutamyltransferase

VFA:

Visceral fat area

VLDL:

Very low density lipoprotein

WFA+-M2BP:

Wisteria floribunda agglutinin-positive Mac-2 binding protein

References

  1. Eguchi E, Iso H, Tanabe N, et al. Healthy lifestyle behaviours and cardiovascular mortality among Japanese men and women: the Japan collaborative cohort study. Eur Heart J. 2012;33:467–77.

    Article  PubMed  Google Scholar 

  2. Survey in Japan Society of Ningen doc in 2012 Japan Society of Ningen Doc. http://www.ningen-dock.jp/wp/common/data/other/ release/dock-genkyou_h24.pdf.

  3. Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007;24:1–6.

    Article  CAS  PubMed  Google Scholar 

  4. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52:1836–46.

    Article  CAS  PubMed  Google Scholar 

  5. Berzigotti A, Garcia-Tsao G, Bosch J, the Portal Hypertension Collaborative Group, et al. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology. 2011;54:555–61.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Alameri HF, Sanai FM, Dukhayll MA, et al. Six-minute walk test to assess functional capacity in chronic liver disease patients. World J Gastoenterol. 2007;13:3996–4001.

    Article  CAS  Google Scholar 

  7. Iritani S, Imai K, Takai K, et al. Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma. J Gastoenterol. 2015;50:323–32.

    Article  CAS  Google Scholar 

  8. Fujiwara N, Nakagawa H, Kudo Y, et al. Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol. 2015;63:131–40.

    Article  CAS  PubMed  Google Scholar 

  9. Hong HC, Hwang SY, Choi HY, et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean sarcopenic obesity study. Hepatology. 2014;59:1772–8.

    Article  CAS  PubMed  Google Scholar 

  10. Lee Y-H, Jung KS, Kim SU, et al. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: nationwide surveys (KNHANES 2008–2011). J Hepatol. 2015;63:486–93.

    Article  PubMed  Google Scholar 

  11. Lee Y-H, Kim SU, Song K, et al. Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: nationwide surveys (KNHANES 2008–2011). Hepatology. 2016;63:776–86.

    Article  CAS  PubMed  Google Scholar 

  12. Farrell GC, Chitturi S, Lau GK, et al. 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 

  13. Sechang Oh, Shida T, Yamagishi K, et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology. 2015;61:1205–15.

    Article  Google Scholar 

  14. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  15. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

    Article  CAS  PubMed  Google Scholar 

  16. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32–6.

    Article  CAS  PubMed  Google Scholar 

  17. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    Article  PubMed  Google Scholar 

  18. Watanabe R, Matsumura M, Munemasa T, et al. Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography. Invest Radiol. 2007;42:643–51.

    Article  CAS  PubMed  Google Scholar 

  19. Iijima H, Moriyasu F, Tsuchiya K, et al. Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic steatohepatitis. Hepatol Res. 2007;37:722–30.

    Article  PubMed  Google Scholar 

  20. Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705–13.

    Article  PubMed  Google Scholar 

  21. Sasso M, Beaugrand M, de Ledinghen V, et al. Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010;36:1825–35.

    Article  PubMed  Google Scholar 

  22. Oh S, Shida T, Onozuka T, et al. Acceleration training for management of non-alcoholic fatty liver disease: a pilot study. Ther Clin Risk Manag. 2014;10:925–36.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kaido T, Ogawa K, Fujimoto Y, et al. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant. 2013;13:1549–56.

    Article  CAS  PubMed  Google Scholar 

  24. Kim H, Hirano H, Edahiro A, et al. Sarcopenia: prevalence and associated factors based on different suggested definitions in community-dwelling older adults. Geriatr Gerontol Int. 2016;16(supple 1):110–22.

    Article  PubMed  Google Scholar 

  25. Newman AB, Kupelian V, Visser M, et al. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc. 2003;51:1602–9.

    Article  PubMed  Google Scholar 

  26. Abbatecola AM, Ferrucci L, Ceda G, et al. Insulin resistance and muscle strength in older persons. J Gerontol A Biol Sci Med Sci. 2005;60A:1278–82.

    Article  Google Scholar 

  27. Cesari M, Kritchevsky SB, Baumgartner RN, et al. Sarcopenia, obesity, and inflammation—results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr. 2005;82:428–34.

    Article  CAS  PubMed  Google Scholar 

  28. Schrager ME, Metter EJ, Simonsick E, et al. Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol. 2007;102:919–25.

    Article  PubMed  Google Scholar 

  29. Kohara K, OchiM Tabara Y, et al. Leptin in sarcopenic visceral obesity: possible link between adipocytes and myocytes. PLoS One. 2011;6:e24633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dyck DJ. Adipokines as regulators of muscle metabolism and insulin sensitivity. Appl Physiol Nutr Metab. 2009;34:396–402.

    Article  CAS  PubMed  Google Scholar 

  31. Sell H, Dietze-Schroeder D, Eckel J. The adipocyte-myocyte axis in insulin resistance. Trends Endocrinol Metab. 2006;17:416–22.

    Article  CAS  PubMed  Google Scholar 

  32. Feldstein AE, Wieckowska A, Lopez AR, et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology. 2009;50:1072–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. She J, Chan HL-Y, Wong GL-H, et al. Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers. J Hepatol. 2012;56:1363–70.

    Article  Google Scholar 

  34. Ikejima K, Honda H, Yoshikawa M, et al. Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology. 2001;34:288–97.

    Article  CAS  PubMed  Google Scholar 

  35. Ikejima K, Takei Y, Honda H, et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology. 2002;122:1399–410.

    Article  CAS  PubMed  Google Scholar 

  36. Imajo K, Fujita K, Yoneda M, et al. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab. 2012;16:44–54.

    Article  CAS  PubMed  Google Scholar 

  37. Pal D, Dasgupta S, Kundu R, et al. Fetuin-A acts an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med. 2012;18:1279–85.

    Article  CAS  PubMed  Google Scholar 

  38. Misu H, Takamura T, Takayama H, et al. A liver-derived secretory protein, selenoprotein-P, causes insulin resistance. Cell Meta. 2010;12:483–95.

    Article  CAS  Google Scholar 

  39. Kharitonenkov A, Larsen P. FGF21 reloaded: challenges of a rapidly growing field. Trends Endocrinol Metab. 2011;22:81–6.

    Article  CAS  PubMed  Google Scholar 

  40. Yarasheski KE, Bhasin S, Sinha-Hikim I, et al. Serum myostatin-immunoreactive protein is increased in 60–92 year old women and men with muscle wasting. J Nutr Health Aging. 2002;6:343–8.

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Takashi Shida, Kentaro Akiyama & Akemi Sawai

  2. Japan Society for the Promotion of Science, Tokyo, Japan

    Kentaro Akiyama

  3. The Center of Sports Medicine and Health Sciences, Tsukuba University Hospital, Ibaraki, Japan

    Sechang Oh

  4. Medical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Tomonori Isobe & Junichi Shoda

  5. Division of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Yoshikazu Okamoto

  6. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Kazunori Ishige & Yuji Mizokami

  7. Division of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Kenji Yamagata & Kojiro Onizawa

  8. Division of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Hironori Tanaka & Hiroko Iijima

  9. Division of Gastroenterology, Takarazuka City Hospital, Takarazuka, Hyogo, Japan

    Hironori Tanaka

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  1. Takashi Shida
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  2. Kentaro Akiyama
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  9. Kenji Yamagata
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Corresponding author

Correspondence to Junichi Shoda.

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Conflict of interest

All authors declare that they have no conflicts of interest.

Funding

This work was supported by in part by Grants-in-Aids for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Nos. 25282212, 26282191, 26293284, 26293297, 26670109, 15K15037, 15K15488, and 16K15188).

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Shida, T., Akiyama, K., Oh, S. et al. Skeletal muscle mass to visceral fat area ratio is an important determinant affecting hepatic conditions of non-alcoholic fatty liver disease. J Gastroenterol 53, 535–547 (2018). https://doi.org/10.1007/s00535-017-1377-3

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  • DOI: https://doi.org/10.1007/s00535-017-1377-3

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