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Fatty acid composition of blood serum and erythrocyte membranes in men with steatosis and steatohepatitis with normal transaminase activity

https://doi.org/10.47093/2218-7332.2024.15.2.48-60

摘要

Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity.

Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied.

Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%.

Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

关于作者

M. Kruchinina
Research Institute of Therapy and Preventive Medicine – branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Novosibirsk State Medical University
俄罗斯联邦


M. Osipenko
Novosibirsk State Medical University
俄罗斯联邦


A. Shestov
Perelman School of Medicine, University of Pennsylvania
美国


M. Parulikova
Research Institute of Therapy and Preventive Medicine – branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
俄罗斯联邦


参考

1. Quek J., Chan K.E., Wong Z.Y., et al. Global prevalence of nonalcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023; 8(1): 20–30. https://doi.org/10.1016/S2468-1253(22)00317-X. Epub 2022 Nov 16. PMID: 36400097

2. Chalasani N., Younossi Z., Lavine J.E., et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018; 67(1): 328–357. https://doi.org/10.1002/hep.29367. Epub 2017 Sep 29. PMID: 28714183

3. Polyzos S.A., Chrysavgis L., Vachliotis I.D., et al. Nonalcoholic fatty liver disease and hepatocellular carcinoma: Insights in epidemiology, pathogenesis, imaging, prevention and therapy. Semin Cancer Biol. 2023 Aug; 93: 20–35. https://doi.org/10.1016/j.semcancer.2023.04.010. Epub 2023 May 4. PMID: 37149203

4. Le M.H., Le D.M., Baez T.C., et al. Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clin Mol Hepatol. 2024 Apr; 30(2): 235–246. https://doi.org/10.3350/cmh.2023.0485. Epub 2024 Jan 26. PMID: 38281814; PMCID: PMC11016479

5. Mantovani A., Petracca G., Beatrice G., et al. Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis. Gut. 2022 Jan; 71(1): 156–162. https://doi.org/10.1136/gutjnl-2020-323082 . Epub 2020 Dec 10. PMID: 33303564

6. Sumida Y., Nakajima A., Itoh Y. Limitations of liver biopsy and noninvasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014 Jan 14; 20(2): 475–485. https://doi.org/10.3748/wjg.v20.i2.475. PMID: 24574716; PMCID: PMC3923022

7. European Association for the Study of the Liver. Electronic address: easloffi ce@easloffi ce.eu; Clinical Practice Guideline Panel; Chair:; EASL Governing Board representative:; Panel members:. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatol. 2021 Sep; 75(3): 659–689. https://doi.org/10.1016/j.jhep.2021.05.025. Epub 2021 Jun 21. PMID: 34166721

8. Uslusoy H.S., Nak S.G., Gülten M., Biyikli Z. Non-alcoholic steatohepatitis with normal aminotransferase values. World J Gastroenterol. 2009 Apr 21; 15(15): 1863–1868. https://doi.org/10.3748/wjg.15.1863. PMID: 19370784; PMCID: PMC2670414

9. Chen Z., Ma Y., Cai J., et al. Serum biomarkers for liver fi brosis. Clin Chim Acta. 2022 Dec 1; 537: 16–25. https://doi.org/10.1016/j.cca.2022.09.022. Epub 2022 Sep 27. PMID: 36174721

10. Munteanu M., Tiniakos D., Anstee Q., et al. Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference. Aliment Pharmacol Ther. 2016 Oct; 44(8): 877–889. https://doi.org/10.1111/apt.13770. Epub 2016 Aug 23. PMID: 27549244; PMCID: PMC5113673

11. Ciećko-Michalska I., Szczepanek M., Wierzbicka-Tutka I., et al. Non-invasive diagnosis of steatosis, infl ammatory changes and liver fi brosis in patients with non-alcoholic fatty liver diseases. Pilot study. Arch Med Sci Atheroscler Dis. 2018 Dec 28; 3: e179–e183. https://doi.org/10.5114/amsad.2018.81184. PMID: 30775610; PMCID: PMC6374567

12. Кручинина М.В., Осипенко М.Ф., Паруликова М.В., Кручинина Э.В. Жирные кислоты мембран эритроцитов в дифференцировании пациентов с жировой болезнью печени алкогольного, неалкогольного и смешанного генеза. Эффективная фармакотерапия. 2023; 19 (43): 28–41. https://doi.org/10.33978/23073586-2023-19-43-28-41. EDN: CQDSQR

13. Yoo W., Gjuka D., Stevenson H.L., et al. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid. PLoS One. 2017 Dec 15; 12(12): e0189965. https://doi.org/10.1371/journal.pone.0189965. PMID: 29244873; PMCID: PMC5731750

14. Shan R., Yin H., Yang W., et al. Infl uencing factors of transient elastography in detecting liver stiffness. Exp Ther Med. 2016 Oct; 12(4): 2302–2306. https://doi.org/10.3892/etm.2016.3617. Epub 2016 Aug 24. Erratum in: Exp Ther Med. 2018 Dec; 16(6): 5425. PMID: 27698728; PMCID: PMC5038607

15. Ma X., Liu S., Zhang J., et al. Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: a systematic review and meta-analysis. BMC Gastroenterol. 2020 Jan 14; 20(1): 10. https://doi.org/10.1186/s12876-020-1165-z. PMID: 31937252; PMCID: PMC6961232

16. Kartsoli S., Kostara C.E., Tsimihodimos V., et al. Lipidomics in non-alcoholic fatty liver disease. World J Hepatol. 2020 Aug 27; 12(8): 436–450. https://doi.org/10.4254/wjh.v12.i8.436. PMID: 32952872; PMCID: PMC7475773

17. Béland-Bonenfant S., Rouland A., Petit J.M., Vergès B. Concise review of lipidomics in nonalcoholic fatty liver disease. Diabetes Metab. 2023 May; 49(3): 101432. https://doi.org/10.1016/j.diabet.2023.101432. Epub 2023 Feb 11. PMID: 36781065

18. Eo H., Valentine R.J. Saturated fatty acid-induced endoplasmic reticulum stress and insulin resistance are prevented by Imoxin in C2C12 myotubes. Front Physiol. 2022 Jul 22; 13: 842819. https://doi.org/10.3389/fphys.2022.842819. PMID: 35936891; PMCID: PMC9355746

19. Wu X., Zhang L., Gurley E., et al. Prevention of free fatty acid-induced hepatic lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology. 2008 Jun; 47(6): 1905–1915. https://doi.org/10.1002/hep.22239. PMID: 18452148

20. Flessa C.M., Nasiri-Ansari N., Kyrou I., et al. Genetic and diet-induced animal models for non-alcoholic fatty liver disease (NAFLD) research. Int J Mol Sci. 2022 Dec 13; 23(24): 15791. https://doi.org/10.3390/ijms232415791. PMID: 36555433; PMCID: PMC9780957

21. Deepak H.B., Shreekrishna N., Sameermahmood Z., et al. An in vitro model of hepatic steatosis using lipid loaded induced pluripotent stem cell derived hepatocyte like cells. J Biol Methods. 2020 Jul 22; 7(3): e135. https://doi.org/10.14440/jbm.2020.330. PMID: 32934967; PMCID: PMC7483829

22. Notarnicola M., Caruso M.G., Tutino V., et al. Signifi cant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD). Lipids Health Dis. 2017 Aug 23; 16(1): 160. https://doi.org/10.1186/s12944-017-0552-0. PMID: 28830448; PMCID: PMC5568099

23. Jenkins B., West J.A., Koulman A. A review of odd-chain fatty acid metabolism and the role of pentadecanoic Acid (c15:0) and heptadecanoic Acid (c17:0) in health and disease. Molecules. 2015 Jan 30; 20(2): 2425–2444. https://doi.org/10.3390/molecules20022425. PMID: 25647578; PMCID: PMC6272531

24. Mayo R., Crespo J., Martínez-Arranz I., et al. Metabolomic-based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts. Hepatol Commun. 2018 May 4; 2(7): 807–820. https://doi.org/10.1002/hep4.1188. PMID: 30027139; PMCID: PMC6049064

25. Lee J.J., Lambert J.E., Hovhannisyan Y., et al. Palmitoleic acid is elevated in fatty liver disease and refl ects hepatic lipogenesis. Am J Clin Nutr. 2015 Jan; 101(1): 34–43. https://doi.org/10.3945/ajcn.114.092262 . Epub 2014 Nov 19. PMID: 25527748; PMCID: PMC4266891

26. Guo R., Chen L., Zhu J., et al. Monounsaturated fatty acid-enriched olive oil exacerbates chronic alcohol-induced hepatic steatosis and liver injury in C57BL/6J mice. Food Funct. 2023 Feb 6; 14 (3):1573– 1583. https://doi.org/10.1039/D2FO03323B. PMID: 36655918

27. Amirkalali B., Sohrabi M.R., Esrafi ly A., et al. Erythrocyte membrane fatty acid profi le & serum cytokine levels in patients with non-alcoholic fatty liver disease. Indian J Med Res. 2018 Apr; 147(4): 352–360. https://doi.org/10.4103/ijmr.IJMR_1065_16. PMID: 29998870; PMCID: PMC6057244

28. Spooner M.H., Jump D.B. Omega-3 fatty acids and nonalcoholic fatty liver disease in adults and children: where do we stand? Curr Opin Clin Nutr Metab Care. 2019 Mar; 22(2): 103–110. https://doi.org/10.1097/MCO.0000000000000539. PMID: 30601174; PMCID: PMC6355343

29. Wang M., Ma L.J., Yang Y., et al. n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review. Crit Rev Food Sci Nutr. 2019; 59(sup1): S116–S129. https://doi.org/10.1080/10408398.2018.1544542. Epub 2018 Dec 22. PMID: 30580553

30. Zhou Y., Orešič M., Leivonen M., et al. Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Clin Gastroenterol Hepatol. 2016 Oct; 14(10): 1463–1472.e6. https://doi.org/10.1016/j.cgh.2016.05.046. Epub 2016 Jun 16. PMID: 27317851

31. Nobili V., Carpino G., Alisi A., et al. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease. PloS one. 2014 Feb 4; 9(2): e88005. https://doi.org/10.1371/journal.pone.0088005. PMID: 24505350; PMCID: PMC3913708

32. Spooner M.H., Jump D.B. Nonalcoholic fatty liver disease and Omega-3 fatty acids: mechanisms and clinical use. Annu Rev Nutr. 2023 Aug 21; 43: 199–223. https://doi.org/10.1146/annurevnutr-061021-030223. Epub 2023 May 19. PMID: 37207355

33. Scorletti E., Bhatia L., McCormick K.G., et al. Effects of purifi ed eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology. 2014 Oct; 60(4): 1211–1221. https://doi.org/10.1002/hep.27289. PMID: 25043514

34. Wang M., Zhang X., Ma L.J., et al. Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease. Biochim Biophys Acta Mol Basis Dis. 2017 Dec; 1863(12): 3190–3201. https://doi.org/10.1016/j.bbadis.2017.08.026. Epub 2017 Aug 25. PMID: 28847514


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1. STROBE Statement—Authors Checklist
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ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)