Skip to main content
Top
Published in: Digestive Diseases and Sciences 7/2019

01-07-2019 | Hepatitis | Original Article

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease

Authors: Bei Gao, Sonja Lang, Yi Duan, Yanhan Wang, Debbie L. Shawcross, Alexandre Louvet, Philippe Mathurin, Samuel B. Ho, Peter Stärkel, Bernd Schnabl

Published in: Digestive Diseases and Sciences | Issue 7/2019

Login to get access

Abstract

Background

Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.

Aims

(1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease.

Methods

We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.

Results

Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality.

Conclusions

Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18.CrossRefPubMed Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18.CrossRefPubMed
3.
go back to reference Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr (Bethesda, Md.). 2015;6:513–540.CrossRef Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr (Bethesda, Md.). 2015;6:513–540.CrossRef
4.
go back to reference Buczynski MW, Dumlao DS, Dennis EA. Thematic review series: proteomics. An integrated omics analysis of eicosanoid biology. J Lipid Res. 2009;50:1015–1038.CrossRefPubMedPubMedCentral Buczynski MW, Dumlao DS, Dennis EA. Thematic review series: proteomics. An integrated omics analysis of eicosanoid biology. J Lipid Res. 2009;50:1015–1038.CrossRefPubMedPubMedCentral
5.
go back to reference Arnold C, Konkel A, Fischer R, Schunck W-H. Cytochrome P450–dependent metabolism of ω-6 and ω-3 long-chain polyunsaturated fatty acids. Pharmacol Rep. 2010;62:536–547.CrossRef Arnold C, Konkel A, Fischer R, Schunck W-H. Cytochrome P450–dependent metabolism of ω-6 and ω-3 long-chain polyunsaturated fatty acids. Pharmacol Rep. 2010;62:536–547.CrossRef
6.
go back to reference Barquissau V, Ghandour RA, Ailhaud G, et al. Control of adipogenesis by oxylipins, GPCRs and PPARs. Biochimie. 2017;136:3–11.CrossRefPubMed Barquissau V, Ghandour RA, Ailhaud G, et al. Control of adipogenesis by oxylipins, GPCRs and PPARs. Biochimie. 2017;136:3–11.CrossRefPubMed
7.
go back to reference Caligiuri SPB, Parikh M, Stamenkovic A, Pierce GN, Aukema HM. Dietary modulation of oxylipins in cardiovascular disease and aging. Am J Physiol Heart Circ Physiol. 2017;313:H903–H918.CrossRefPubMed Caligiuri SPB, Parikh M, Stamenkovic A, Pierce GN, Aukema HM. Dietary modulation of oxylipins in cardiovascular disease and aging. Am J Physiol Heart Circ Physiol. 2017;313:H903–H918.CrossRefPubMed
9.
go back to reference Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871.CrossRef Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871.CrossRef
10.
go back to reference Yeung J, Hawley M, Holinstat M. The expansive role of oxylipins on platelet biology. J Mol Med (Berlin, Germany). 2017;95:575–588.CrossRef Yeung J, Hawley M, Holinstat M. The expansive role of oxylipins on platelet biology. J Mol Med (Berlin, Germany). 2017;95:575–588.CrossRef
11.
go back to reference Wagner D, Westover K, Simmons DL. Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever. Clin Infect Dis. 2000;31:S211–S218.CrossRefPubMed Wagner D, Westover K, Simmons DL. Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever. Clin Infect Dis. 2000;31:S211–S218.CrossRefPubMed
12.
go back to reference Liu MC, Dubé LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: A 6-month randomized multicenter trial. J Allergy Clin Immunol. 1996;98:859–871.CrossRefPubMed Liu MC, Dubé LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: A 6-month randomized multicenter trial. J Allergy Clin Immunol. 1996;98:859–871.CrossRefPubMed
13.
go back to reference Zhang W, Zhong W, Sun Q, Sun X, Zhou Z. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Sci Rep. 2017;7:8976.CrossRefPubMedPubMedCentral Zhang W, Zhong W, Sun Q, Sun X, Zhou Z. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Sci Rep. 2017;7:8976.CrossRefPubMedPubMedCentral
14.
go back to reference Feldstein AE, Lopez R, Tamimi TA-R, et al. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Lipid Res. 2010;51:3046–3054.CrossRefPubMedPubMedCentral Feldstein AE, Lopez R, Tamimi TA-R, et al. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Lipid Res. 2010;51:3046–3054.CrossRefPubMedPubMedCentral
15.
go back to reference Ball SA, Tennen H, Poling JC, Kranzler HR, Rounsaville BJ. Personality, temperament, and character dimensions and the DSM-IV personality disorders in substance abusers. J Abnorm Psychol. 1997;106:545–553.CrossRefPubMed Ball SA, Tennen H, Poling JC, Kranzler HR, Rounsaville BJ. Personality, temperament, and character dimensions and the DSM-IV personality disorders in substance abusers. J Abnorm Psychol. 1997;106:545–553.CrossRefPubMed
17.
go back to reference Nguyen-Khac E, Thiele M, Voican C, et al. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2018;3:614–625.CrossRefPubMed Nguyen-Khac E, Thiele M, Voican C, et al. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2018;3:614–625.CrossRefPubMed
19.
go back to reference Buzzetti E, Lombardi R, De Luca L, Tsochatzis EA. Noninvasive assessment of fibrosis in patients with nonalcoholic fatty liver disease. Int J Endocrinol. 2015;2015:343828.CrossRefPubMedPubMedCentral Buzzetti E, Lombardi R, De Luca L, Tsochatzis EA. Noninvasive assessment of fibrosis in patients with nonalcoholic fatty liver disease. Int J Endocrinol. 2015;2015:343828.CrossRefPubMedPubMedCentral
20.
go back to reference Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with non-alcoholic fatty liver disease. Gastroenterology. 2019;156:1717–1730.CrossRefPubMed Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with non-alcoholic fatty liver disease. Gastroenterology. 2019;​156:1717–1730.CrossRefPubMed
21.
go back to reference Caussy C, Alquiraish MH, Nguyen P, et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology. 2018;67:1348–1359.CrossRefPubMedPubMedCentral Caussy C, Alquiraish MH, Nguyen P, et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology. 2018;67:1348–1359.CrossRefPubMedPubMedCentral
22.
go back to reference Karlas T, Petroff D, Sasso M, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66:1022–1030.CrossRefPubMed Karlas T, Petroff D, Sasso M, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66:1022–1030.CrossRefPubMed
23.
go back to reference Leclercq S, Matamoros S, Cani PD, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci USA. 2014;111:E4485–E4493.CrossRefPubMed Leclercq S, Matamoros S, Cani PD, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci USA. 2014;111:E4485–E4493.CrossRefPubMed
24.
go back to reference Shearer GC, Harris WS, Pedersen TL, Newman JW. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters. J Lipid Res. 2010;51:2074–2081.CrossRefPubMedPubMedCentral Shearer GC, Harris WS, Pedersen TL, Newman JW. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters. J Lipid Res. 2010;51:2074–2081.CrossRefPubMedPubMedCentral
25.
go back to reference Luria A, Weldon SM, Kabcenell AK, et al. Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem. 2007;282:2891–2898.CrossRefPubMed Luria A, Weldon SM, Kabcenell AK, et al. Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice. J Biol Chem. 2007;282:2891–2898.CrossRefPubMed
26.
go back to reference Barupal DK, Fiehn O. Chemical similarity enrichment analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets. Sci Rep. 2017;7:14567.CrossRefPubMedPubMedCentral Barupal DK, Fiehn O. Chemical similarity enrichment analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets. Sci Rep. 2017;7:14567.CrossRefPubMedPubMedCentral
27.
go back to reference Warner DR, Liu H, Ghosh Dastidar S, et al. Ethanol and unsaturated dietary fat induce unique patterns of hepatic ω-6 and ω-3 PUFA oxylipins in a mouse model of alcoholic liver disease. PloS One. 2018;13:e0204119.CrossRefPubMedPubMedCentral Warner DR, Liu H, Ghosh Dastidar S, et al. Ethanol and unsaturated dietary fat induce unique patterns of hepatic ω-6 and ω-3 PUFA oxylipins in a mouse model of alcoholic liver disease. PloS One. 2018;13:e0204119.CrossRefPubMedPubMedCentral
28.
go back to reference Lazic M, Inzaugarat ME, Povero D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis. PloS one. 2014;9:e107658.CrossRefPubMedPubMedCentral Lazic M, Inzaugarat ME, Povero D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis. PloS one. 2014;9:e107658.CrossRefPubMedPubMedCentral
29.
go back to reference Puri P, Xu J, Vihervaara T, et al. Alcohol produces distinct hepatic lipidome and eicosanoid signature in lean and obese. J Lipid Res. 2016;57:1017–1028.CrossRefPubMedPubMedCentral Puri P, Xu J, Vihervaara T, et al. Alcohol produces distinct hepatic lipidome and eicosanoid signature in lean and obese. J Lipid Res. 2016;57:1017–1028.CrossRefPubMedPubMedCentral
30.
go back to reference Puri P, Wiest MM, Cheung O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.). 2009;50:1827–1838.CrossRef Puri P, Wiest MM, Cheung O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.). 2009;50:1827–1838.CrossRef
31.
go back to reference Zein CO, Lopez R, Fu X, et al. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology (Baltimore, Md.). 2012;56:1291–1299.CrossRef Zein CO, Lopez R, Fu X, et al. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology (Baltimore, Md.). 2012;56:1291–1299.CrossRef
32.
go back to reference Kirpich IA, Feng W, Wang Y, et al. The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic toll-like receptor expression in a mouse model of alcoholic liver disease. Alcohol Clin Exp Res. 2012;36:835–846.CrossRefPubMed Kirpich IA, Feng W, Wang Y, et al. The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic toll-like receptor expression in a mouse model of alcoholic liver disease. Alcohol Clin Exp Res. 2012;36:835–846.CrossRefPubMed
33.
go back to reference Noverr MC, Erb-Downward JR, Huffnagle GB. Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev. 2003;16:517–533.CrossRefPubMedPubMedCentral Noverr MC, Erb-Downward JR, Huffnagle GB. Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev. 2003;16:517–533.CrossRefPubMedPubMedCentral
34.
go back to reference Tsitsigiannis DI, Keller NP. Oxylipins as developmental and host–fungal communication signals. Trends Microbiol. 2007;15:109–118.CrossRef Tsitsigiannis DI, Keller NP. Oxylipins as developmental and host–fungal communication signals. Trends Microbiol. 2007;15:109–118.CrossRef
Metadata
Title
Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease
Authors
Bei Gao
Sonja Lang
Yi Duan
Yanhan Wang
Debbie L. Shawcross
Alexandre Louvet
Philippe Mathurin
Samuel B. Ho
Peter Stärkel
Bernd Schnabl
Publication date
01-07-2019
Publisher
Springer US
Keyword
Hepatitis
Published in
Digestive Diseases and Sciences / Issue 7/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05638-y

Other articles of this Issue 7/2019

Digestive Diseases and Sciences 7/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.