Skip to main content

Advertisement

SpringerLink
Log in

Plasma Free Myristic Acid Proportion Is a Predictor of Nonalcoholic Steatohepatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background/Aims

Serum free fatty acid (FFA) composition and abnormal fatty acid metabolism have been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, we determined if the serum FFA composition can provide accurate diagnosis of NASH.

Methods

We compared fasting serum FFA compositions in 20 patients with simple steatosis to those in 77 patients with NASH, including 65 patients with early-stage NASH.

Results

By univariate analysis, the proportions of serum free myristic acid (P = 0.002) and palmitoleic acid (P = 0.033) and the stearoyl CoA desaturase (SCD)-1 index (P = 0.047) were significantly elevated in NASH patients in comparison to patients with simple steatosis. Only the serum free myristic acid proportion was significantly elevated in the early-stage NASH group in comparison to the simple steatosis group (P = 0.003). Multiple logistic regression analysis demonstrated that the serum free myristic acid proportion was significantly elevated in all patients with NASH (P = 0.011) and the subset of patients with early-stage NASH (P = 0.012) in comparison to those with simple steatosis. The area under the curve (AUC) for the serum free myristic acid proportion was 0.734 to detect NASH and 0.719 to detect early-stage NASH in comparison to simple steatosis.

Conclusions

Serum free myristic acid proportion could be a useful independent predictor to differentiate NASH from simple steatosis.

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

Similar content being viewed by others

Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

SFA:

Saturated fatty acid

FFA:

Free fatty acid

MUFA:

Monounsaturated fatty acid

PUFA:

Polyunsaturated fatty acid

SCD:

Stearoyl-CoA desaturase

SD:

Standard deviation

ANOVA:

Analysis of variance

ROC:

Receiver operating characteristic

BMI:

Body mass index

HOMA-IR:

Homeostasis model assessment for insulin resistance

IRI:

Immunoreactive insulin

AUC:

Area under the curve

PPV:

Positive predictive value

NPV:

Negative predictive value

TLR4:

Toll-like receptor 4

References

  1. Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143:722–728.

    PubMed  CAS  Google Scholar 

  2. 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 

  3. Neuschwander-Tetri BA. Fatty liver and the metabolic syndrome. Curr Opin Gastroenterol. 2007;23:193–198.

    Article  PubMed  CAS  Google Scholar 

  4. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liv Dis. 2001;21:17–26.

    Article  CAS  Google Scholar 

  5. Adams LA, Lymp JF, St Sauver JS, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–121.

    Article  PubMed  Google Scholar 

  6. Tsochatzis E, Papatheodoridis GV, Manesis EK, Kafiri G, Tiniakos DG, Archimandriris AJ. Metabolic syndrome is associated with severe fibrosis in chronic viral hepatitis and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2008;27:80–89.

    Article  PubMed  CAS  Google Scholar 

  7. Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology. 2003;37:909–916.

    Article  PubMed  CAS  Google Scholar 

  8. Cazanave SC, Gores GJ. Mechanisms and clinical implications of hepatocyte lipoapoptosis. Clin Lipidol. 2010;5:71–85.

    Article  PubMed  Google Scholar 

  9. Malhi H, Gores GJ. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:360–369.

    Article  PubMed  CAS  Google Scholar 

  10. Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology. 2006;147:943–951.

    Article  PubMed  CAS  Google Scholar 

  11. Masterton GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids–a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010;31:679–692.

    Article  PubMed  CAS  Google Scholar 

  12. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21:3–16.

    Article  PubMed  CAS  Google Scholar 

  13. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–1419.

    Article  PubMed  CAS  Google Scholar 

  14. Miwa H, Yamamoto M, Nishida T, Nunoi K, Kikuchi M. High-performance liquid chromatography analysis of serum long-chain fatty acids by direct derivatization method. J Chromatogr. 1987;416:237–245.

    Article  PubMed  CAS  Google Scholar 

  15. Youden WJ. An index for rating diagnostic tests. Cancer. 1950;3:32–35.

    Article  PubMed  CAS  Google Scholar 

  16. Perkins NJ, Schisterman EF. The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163:670–675.

    Article  PubMed  Google Scholar 

  17. Gentile CL, Pagliassotti MJ. The role of fatty acids in the development and progression of nonalcoholic fatty liver disease. J Nutr Biochem. 2008;19:567–576.

    Article  PubMed  CAS  Google Scholar 

  18. Neuschwander-Tetri BA. Nontriglyceride hepatic lipotoxicity: the new paradigm for the pathogenesis of NASH. Curr Gastroenterol Rep. 2010;12:49–56.

    Article  PubMed  Google Scholar 

  19. Wang S, MA A, Song S, Quan Q, Zhao X, Zheng X. Fasting serum free fatty acid composition, waist/hip ratio and insulin activity in essential hypertensive patients. Hypertens Res. 2008;31:623–632.

    Article  PubMed  Google Scholar 

  20. Jensen RG, Ferris AM, Lammi-Keefe CJ, Henderson RA. Lipids of bovine and human milks: a comparison. J Dairy Sci. 1990;73:223–240.

    Article  PubMed  CAS  Google Scholar 

  21. Rioux V, Catheline D, Bouriel M, Legrand P. Dietary myristic acid at physiologically relevant levels increases the tissue content of C20:5 n-3 and C20:3 n-6 in the rat. Reprod Nutr Dev. 2005;45:599–612.

    Article  PubMed  CAS  Google Scholar 

  22. Debois D, Bralet MP, Le Naour FL, Brunelle A, Laprevote O. In situ lipidomic analysis of nonalcoholic fatty liver by cluster TOF-SIMS imaging. Anal Chem. 2009;81:2823–2831.

    Article  PubMed  CAS  Google Scholar 

  23. Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–845.

    Article  PubMed  CAS  Google Scholar 

  24. Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008;134:933–944.

    Article  PubMed  CAS  Google Scholar 

  25. Akazawa Y, Cazanave S, Mott JL, et al. Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis. J Hepatol. 2010;52:586–593.

    Article  PubMed  CAS  Google Scholar 

  26. Kotronen A, Seppanen-Laakso T, Westerbacka J, et al. Hepatic stearoyl-CoA desaturase (SCD)-1 activity and deacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes. 2009;58:203–208.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Conflict of interest

All the authors certify that no conflicts of interest exist.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Kengo Tomita, Toshiaki Teratani, Takahiro Suzuki, Hirotoshi Ebinuma & Toshifumi Hibi

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa-shi, Saitama, 359-8513, Japan

    Kengo Tomita, Ryota Hokari & Soichiro Miura

  3. Health Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hirokazu Yokoyama

  4. Department of Pathology, Kawasaki Municipal Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0013, Japan

    Rie Irie

  5. Graduate School of Pharmaceutical Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan

    Hidetsugu Saito

Authors
  1. Kengo Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshiaki Teratani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirokazu Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takahiro Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rie Irie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirotoshi Ebinuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hidetsugu Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ryota Hokari
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Soichiro Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toshifumi Hibi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshifumi Hibi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomita, K., Teratani, T., Yokoyama, H. et al. Plasma Free Myristic Acid Proportion Is a Predictor of Nonalcoholic Steatohepatitis. Dig Dis Sci 56, 3045–3052 (2011). https://doi.org/10.1007/s10620-011-1712-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-011-1712-0

Keywords

Search

Navigation