dc.contributor.author |
Du Plessis, Johannie
|
|
dc.contributor.author |
Van Pelt, Jos
|
|
dc.contributor.author |
Korf, Hannelie
|
|
dc.contributor.author |
Mathieu, Chantal
|
|
dc.contributor.author |
Van der Schueren, Bart
|
|
dc.contributor.author |
Lannoo, Matthias
|
|
dc.contributor.author |
Oyen, Tom
|
|
dc.contributor.author |
Topal, Baki
|
|
dc.contributor.author |
Fetter, Gary
|
|
dc.contributor.author |
Nayler, Simon
|
|
dc.contributor.author |
Van der Merwe, Tessa
|
|
dc.contributor.author |
Windmolders, Petra
|
|
dc.contributor.author |
Van Gaal, Luc
|
|
dc.contributor.author |
Verrijken, An
|
|
dc.contributor.author |
Hubens, Guy
|
|
dc.contributor.author |
Gericke, Martin
|
|
dc.contributor.author |
Cassiman, David
|
|
dc.contributor.author |
Francque, Sven
|
|
dc.contributor.author |
Nevens, Frederik
|
|
dc.contributor.author |
Van der Merwe, Schalk
|
|
dc.date.accessioned |
2016-06-20T05:55:37Z |
|
dc.date.issued |
2015-09 |
|
dc.description.abstract |
BACKGROUND & 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.department |
Internal Medicine |
en_ZA |
dc.description.embargo |
2016-09-30 |
|
dc.description.librarian |
hb2016 |
en_ZA |
dc.description.sponsorship |
Schalk 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.uri |
http://www.journals.elsevier.com/gastroenterology |
en_ZA |
dc.identifier.citation |
Du 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.issn |
0016-5085 (print) |
|
dc.identifier.issn |
1528-0012 (online) |
|
dc.identifier.other |
10.1053/j.gastro.2015.05.044 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/53243 |
|
dc.language.iso |
en |
en_ZA |
dc.publisher |
Elsevier |
en_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.subject |
Gene expression |
en_ZA |
dc.subject |
IL8 |
en_ZA |
dc.subject |
Immune regulation |
en_ZA |
dc.subject |
Inflammatory response |
en_ZA |
dc.subject |
Nonalcoholic fatty liver disease (NAFLD) |
en_ZA |
dc.subject |
Subcutaneous adipose tissue (SAT) |
en_ZA |
dc.subject |
Visceral adipose tissue (VAT) |
en_ZA |
dc.subject |
Adipocyte tissue macrophages (ATMs) |
en_ZA |
dc.subject |
Obesity |
en_ZA |
dc.subject |
Nonalcoholic steatohepatitis (NASH) |
en_ZA |
dc.title |
Association of Adipose tissue inflammation with histologic severity of nonalcoholic fatty liver disease |
en_ZA |
dc.type |
Postprint Article |
en_ZA |