Association of Adipose tissue inflammation with histologic severity of nonalcoholic fatty liver disease

dc.contributor.authorDu Plessis, Johannie
dc.contributor.authorVan Pelt, Jos
dc.contributor.authorKorf, Hannelie
dc.contributor.authorMathieu, Chantal
dc.contributor.authorVan der Schueren, Bart
dc.contributor.authorLannoo, Matthias
dc.contributor.authorOyen, Tom
dc.contributor.authorTopal, Baki
dc.contributor.authorFetter, Gary
dc.contributor.authorNayler, Simon
dc.contributor.authorVan der Merwe, Tessa
dc.contributor.authorWindmolders, Petra
dc.contributor.authorVan Gaal, Luc
dc.contributor.authorVerrijken, An
dc.contributor.authorHubens, Guy
dc.contributor.authorGericke, Martin
dc.contributor.authorCassiman, David
dc.contributor.authorFrancque, Sven
dc.contributor.authorNevens, Frederik
dc.contributor.authorVan der Merwe, Schalk
dc.date.accessioned2016-06-20T05:55:37Z
dc.date.issued2015-09
dc.description.abstractBACKGROUND & AIMS : The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the obesity pandemic. We analyzed the transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and phenotypes and functional characteristics of adipocyte tissue macrophages (ATMs), in obese patients undergoing bariatric surgery. METHODS : We collected anthropometric data; plasma samples; and SAT, VAT, and liver tissues from 113 obese patients undergoing bariatric surgery at academic hospitals in Europe (Antwerp and Leuven) and South Africa. Based on clinical and histologic features, patients were assigned to the following groups: obese, NAFLD, nonalcoholic steatohepatitis (NASH), or NASH with fibrosis. Microarray analyses were performed to identify genes expressed differentially among groups. We measured levels of cytokines and chemokines in plasma samples and levels of RNAs in adipose tissues by quantitative reverse-transcription polymerase chain reaction. ATMs were isolated from patients and 13 lean individuals undergoing cholecystectomy (controls), analyzed by flow cytometry, and cultured; immunophenotypes and levels of cytokines and chemokines in supernatants were determined. RESULTS : We observed increased expression of genes that regulate inflammation in adipose tissues from patients with NAFLD and NASH; expression of these genes increased as disease progressed from NAFLD to NASH. We found 111 genes associated with inflammation that were expressed differentially between VAT and SAT. Serum levels of interleukin 8, chemokine (C-C motif) ligand 3, and tumor necrosis factor-a correlated with liver inflammation and NAFLD activity score. We developed 2 models that could be used to determine patients’ liver histology based on gene expression in VAT and SAT. Flow cytometry showed increased proportions of CD11cþCD206þ and CCR2þ macrophages in VAT from patients with NASH, and supernatants of cultured macrophages had increased levels of cytokines and chemokines compared with controls. CONCLUSIONS : VAT and SAT from patients with NAFLD and NASH have an increased expression of genes that regulate inflammation, and ATM produce increased levels of inflammatory cytokines, compared with adipose tissues from controls. We identified an expression profile of 5 genes in SAT that accurately predict liver histology in these patients. Transcript profiling: accession numbers: GSE58979 and GSE59045.en_ZA
dc.description.departmentInternal Medicineen_ZA
dc.description.embargo2016-09-30
dc.description.librarianhb2016en_ZA
dc.description.sponsorshipSchalk van der Merwe, Chantal Mathieu, Frederik Nevens, David Cassiman, and Sven Francque are recipients of the Flanders fund for scientific research (FWO klinisch mandaat), and Hannelie Korf is a recipient of the FWO postdoctoral mandate. Research at the Department of Endocrinology, Diabetology and Metabolism and the Department of Gastroenterology and Hepatology of the Antwerp University Hospital (Belgium) was supported by the European Union: FP6 (HEPADIP contract LSHM-CT-2005-018734) and FP7-HEALTH (RESOLVE no. 305707). Supported by a fellowship from the South African Gastroenterology Association and a scholarship from the European Association for the Study of the Liver (J.d.P.). This research also was supported by a research grant from the Gastro foundation of South Africa. The authors specifically acknowledge the support of Dr. Chris Kassianides. Also funded in part by a grant from the Deutsche Forschungsgemeinschaft DFG-SFB 1052/1: Obesity Mechanisms (projects A04) and by the Helmholtz Alliance Imaging and Curing Environmental Metabolic Disease through the Initiative and Networking Fund of the Helmholtz Association (M.G.).en_ZA
dc.description.urihttp://www.journals.elsevier.com/gastroenterologyen_ZA
dc.identifier.citationDu Plessis, J, Van Pelt, J, Korf, H, Mathieu, C, Van der Schueren, B, Lannoo, M, Oyen, T, Topal, B, Fetter, G, Nayler, S, Van der Merwe, T, Windmolders, P, Van Gaal, L, Verrijken, A, Hubens, G, Gericke, M, Cassiman, D, Francque, S, Nevens, F & Van der Merwe, S 2015, 'Association of Adipose tissue inflammation with histologic severity of nonalcoholic fatty liver disease', Gastroenterology, vol. 149, pp. 635-648.en_ZA
dc.identifier.issn0016-5085 (print)
dc.identifier.issn1528-0012 (online)
dc.identifier.other10.1053/j.gastro.2015.05.044
dc.identifier.urihttp://hdl.handle.net/2263/53243
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2015 by the AGA Institute. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Gastroenterology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Gastroenterology, vol. 149, pp. 635-648, 2015. doi : 10.1053/j.gastro.2015.05.044.en_ZA
dc.subjectGene expressionen_ZA
dc.subjectIL8en_ZA
dc.subjectImmune regulationen_ZA
dc.subjectInflammatory responseen_ZA
dc.subjectNonalcoholic fatty liver disease (NAFLD)en_ZA
dc.subjectSubcutaneous adipose tissue (SAT)en_ZA
dc.subjectVisceral adipose tissue (VAT)en_ZA
dc.subjectAdipocyte tissue macrophages (ATMs)en_ZA
dc.subjectObesityen_ZA
dc.subjectNonalcoholic steatohepatitis (NASH)en_ZA
dc.titleAssociation of Adipose tissue inflammation with histologic severity of nonalcoholic fatty liver diseaseen_ZA
dc.typePostprint Articleen_ZA

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