Association of fibroblast growth factor 21 with alcohol consumption and alcohol liver cirrhosis

Springer Science and Business Media LLC - Tập 35 Số 3 - Trang 140-146 - 2021
Jolana Wagner-Skacel1, Angela Horvath2, Philipp Grande2, Julian Wenninger3, Franziska Matzer1, Christian Fazekas1, Sabrina Mörkl4, Andreas Meinitzer5, Vanessa Stadlbauer2
1Department of Medical Psychology and Psychotherapy, Medical University of Graz (MUG), Auenbruggerplatz 3, 8036, Graz, Austria
2Division of Gastroenterology and Hepatology, Medical University of Graz (MUG), Graz, Austria
3Department of Child and Adolescent Psychiatry, LKH Graz II, Graz, Austria
4Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz (MUG), Graz, Austria
5Department of Clinical and Chemical Laboratory Diagnostics, Medical University of Graz (MUG), Graz, Austria

Tóm tắt

SummaryBackgroundFibroblast growth factor 21 (FGF21) is produced in the liver and binds to different complex receptor/coreceptor systems. Besides many other processes, FGF21 regulates the intake of simple sugars and alcohol. Increased levels of FGF21 decrease harmful alcohol intake in mice. To increase our understanding on the relationship between FGF21 and alcohol intake in humans, we aimed to measure FGF21 levels in patients with alcoholic liver cirrhosis (ALC) in comparison to patients with nonalcoholic liver cirrhosis (NALC) and healthy persons based on their present alcohol consumption.MethodsAlcohol intake was verified by urinary ethyl glucuronide (uETG) levels, eating and drinking behaviour by a Food Frequency Questionnaire and FGF 21 plasma levels were determined by ELISA in 96 persons (ALCn = 41; NALCn = 34; healthyn = 21).ResultsBoth ALC and NALC patients with elevated ETG levels (≥0.5 μg/ml; indicating alcohol consumption in the last 12–72 h) showed significantly higher FGF21 plasma levels in comparison to patients with negative ETG levels. Eating behaviour did not have an impact on FGF21 plasma levels.ConclusionsIncreased FGF21 levels in patients with recent alcohol consumption (verified by ETG) confirmed the first part of the liver–brain endocrine axis: alcohol consumption was associated with increased FGF21 levels. We could not confirm that elevated FGF21 levels were associated with reduced alcohol intake as a result. That points towards a pathology in this pathway, which might be caused by a malfunction of β‑Klotho or FGF receptors according to other studies and chronic alcohol dependency. Further research is required to clarify these pathologies, which may open new pharmacological treatment for patients with alcohol use disorder and alcohol dependence.

Từ khóa


Tài liệu tham khảo

Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H et al. Epidemiology of DSM‑5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. Jama Psychiatry. 2015;72(8):757–66.

Karlsen TH, Pimpin L, Webber L, Saxton J, Corbould E, Flood J. Hepahealth projekt report. European Association for the Study of the Liver. 2018. www.easl.eu. Accessed: November 2018.

World Health Organization. Global status report on alcohol and health 2014. Geneva: World Health Organization; 2014.

World Health Organization Regional Office for Europe. European detailed mortality database. Geneva: World Health Organization; 2014.

Bachmayer S, Strizek J, Hojni M, Uhl A. Handbuch Alkohol – Österreich. Band 1: Statistiken und Berechnungsgrundlagen 2019. Wien: Gesundheit Österreich GmbH; 2020. https://broschuerenservice.sozialministerium.at/Home/Download?publicationId=598.

Kim S, Kwok S, Mayes LC, Potenza MN, Rutherford HJ, Strathearn L. Early adverse experience and substance addiction: dopamine, oxytocin, and glucocorticoid pathways. Ann NY Acad Sci. 2017;1394(1):74.

Song P, Zechner C, Hernandez G, Cánovas J, Xie Y, Sondhi V et al. The hormone FGF21 stimulates water drinking in response to ketogenic diet and alcohol. Cell Metab. 2018;27(6):1338–47.

Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y et al. FGF21 regulates sweet and alcohol preference. Cell Metab. 2016;23(2):344–9.

Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235–53.

Fon Tacer K, Bookout AL, Ding X. Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. 2010;24(10):2050–64.

Coskun T, Bina HA, Schneider MA, Dunbar JD. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008;149(12):6018–27.

Potthoff M, Kliewer S, Mangelsdorf D. Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev. 2016;26(4):312–24.

Owen BM, Bookout AL, Ding X, Lin VY, Atkin SD, Gautron L et al. FGF21 contributes to neuroendocrine control of female reproduction. Nat Med. 2013;19(9):1153–6.

Bernardin F, Maheut-Bosser A, Paille F. Cognitive impairments in alcohol-dependent subjects. Front Psychiatry. 2014;5:78.

Zhao C, Liu Y, Xiao J, Liu L, Chen S, Mohammadi M et al. FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice. J Lipid Res. 2015;56(8):1481–91.

Glass GV, Peckham PD, Sanders JR. Consequences of failure to meet assumptions underlying the fixed effects analyses of variance and covariance. Rev Educ Res. 1972;42(3):237–88.

Salkind NJ. Encyclopedia of research design. Vol. 2. Los Angeles: SAGE; 2010.

Pagano RR. Understanding statistics in the behavioral sciences. 9th ed. Belmont: Thomson Wadsworth; 2010.

Schumanna G, Liub C, O’Reillya P, Gaoe H, Songg P, Xu B. KLB is associated with alcohol drinking, and its gene product β‑Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci USA. 2016;113(50):14372–7.

Dawson DA, Grant BF, Stinson FS, Zhou Y. Effectiveness of the derived Alcohol Use Disorders Identification Test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population. Alcohol Clin Exp Res. 2005;29(5):844–54.

Enoch MA. The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology. 2011;214(1):17–31.

Jentsch JD, Ashenhurst JR, Cervantes MC, James AS, Groman SM, Pennington ZT. Dissecting impulsivity and its relationships to drug addictions. Ann NY Acad Sci. 2014;1327:1.

Bernardin F, Maheut-Bosser A, Paille F. Cognitive impairments in alcohol-dependent subjects. Front Psychiatry. 2014;5:78.

Dai X, Thavundayil J, Santella S, Gianoulakis C. Response of the HPA-axis to alcohol and stress as a function of alcohol dependence and family history of alcoholism. Psychoneuroendocrinology. 2007;32(3):293–305.

Tsigos C, Chrousos GP. Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–71.

De Kloet ER, Derijk R. Signaling pathways in brain involved in predisposition and pathogenesis of stress-related disease: genetic and kinetic factors affecting the MR/GR balance. Ann NY Acad Sci. 2004;1032(1):14–34.

Lovallo WR. Cortisol secretion patterns in addiction and addiction risk. Int J Psychophysiol. 2006;59(3):195–202.

Bernardin F, Maheut-Bosser A, Paille F. Cognitive impairments in alcohol-dependent subjects. Front Psychiatry. 2014;5:78.

Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Tập 35 Số 3

140-146

Thông tin tác giả