The University of Southampton
University of Southampton Institutional Repository

Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD

Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD
Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD
Background and aims: subcutaneous adipose tissue (SAT) dysfunction contributes to NAFLD pathogenesis and may be influenced by the gut microbiota. Whether transcript profiles of SAT are associated with liver fibrosis and are influenced by synbiotic treatment (that changes the gut microbiome) is unknown. We investigated: (a) whether the presence of clinically significant, ≥F2 liver fibrosis associated with adipose tissue (AT) dysfunction, differential gene expression in SAT, and/or a marker of tissue fibrosis (Composite collagen gene expression (CCGE)); and (b) whether synbiotic treatment modified markers of AT dysfunction and the SAT transcriptome.

Methods: sixty-two patients with NAFLD (60 % men) were studied before and after 12 months of treatment with synbiotic or placebo and provided SAT samples. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. RNA-sequencing and histological analysis of SAT were performed to determine differential gene expression, CCGE and the presence of collagen fibres. Regression modelling and receiver operator characteristic curve analysis were used to test associations with, and risk prediction for, ≥F2 liver fibrosis.

Results: patients with ≥F2 liver fibrosis (n = 24) had altered markers of AT dysfunction and a SAT gene expression signature characterised by enrichment of inflammatory and extracellular matrix-associated genes, compared to those with
Conclusion: a differential gene expression signature in SAT associates with ≥F2 liver fibrosis is explained by a measure of systemic insulin resistance and is not changed by synbiotic treatment. SAT CCGE values are a good predictor of ≥F2 liver fibrosis in NAFLD.
Adipose tissue, Gut microbiome, Liver fibrosis, NAFLD, Synbiotic, Transcriptome
0026-0495
Bilson, Josh
a99f9320-335c-47c8-bf30-07df48a5467d
Oquendo, Carolina J.
7ac6cb48-5df8-4d22-9907-46dc8f4d4b18
Read, James
ab0a5309-095b-4db1-ab90-913f2847c81e
Scorletti, Eleonora
f8da98be-ec6c-4ad6-89ca-1afe37269485
Afolabi, Paul R.
757e7f01-664c-493e-bc51-c6a2c933dc22
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Bindels, Laure B.
0b334e2b-6029-4482-bfa4-65c62ca91fb5
Targher, Giovanni
f3ab808c-fdd9-4040-bc1e-40f7b4417717
Mahajan, Sumeet
b131f40a-479e-4432-b662-19d60d4069e9
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Bilson, Josh
a99f9320-335c-47c8-bf30-07df48a5467d
Oquendo, Carolina J.
7ac6cb48-5df8-4d22-9907-46dc8f4d4b18
Read, James
ab0a5309-095b-4db1-ab90-913f2847c81e
Scorletti, Eleonora
f8da98be-ec6c-4ad6-89ca-1afe37269485
Afolabi, Paul R.
757e7f01-664c-493e-bc51-c6a2c933dc22
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Bindels, Laure B.
0b334e2b-6029-4482-bfa4-65c62ca91fb5
Targher, Giovanni
f3ab808c-fdd9-4040-bc1e-40f7b4417717
Mahajan, Sumeet
b131f40a-479e-4432-b662-19d60d4069e9
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85

Bilson, Josh, Oquendo, Carolina J., Read, James, Scorletti, Eleonora, Afolabi, Paul R., Lord, Jenny, Bindels, Laure B., Targher, Giovanni, Mahajan, Sumeet, Baralle, Diana, Calder, Philip C., Byrne, Christopher D. and Sethi, Jaswinder K. (2024) Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD. Metabolism, 151, [155759]. (doi:10.1016/j.metabol.2023.155759).

Record type: Article

Abstract

Background and aims: subcutaneous adipose tissue (SAT) dysfunction contributes to NAFLD pathogenesis and may be influenced by the gut microbiota. Whether transcript profiles of SAT are associated with liver fibrosis and are influenced by synbiotic treatment (that changes the gut microbiome) is unknown. We investigated: (a) whether the presence of clinically significant, ≥F2 liver fibrosis associated with adipose tissue (AT) dysfunction, differential gene expression in SAT, and/or a marker of tissue fibrosis (Composite collagen gene expression (CCGE)); and (b) whether synbiotic treatment modified markers of AT dysfunction and the SAT transcriptome.

Methods: sixty-two patients with NAFLD (60 % men) were studied before and after 12 months of treatment with synbiotic or placebo and provided SAT samples. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. RNA-sequencing and histological analysis of SAT were performed to determine differential gene expression, CCGE and the presence of collagen fibres. Regression modelling and receiver operator characteristic curve analysis were used to test associations with, and risk prediction for, ≥F2 liver fibrosis.

Results: patients with ≥F2 liver fibrosis (n = 24) had altered markers of AT dysfunction and a SAT gene expression signature characterised by enrichment of inflammatory and extracellular matrix-associated genes, compared to those with
Conclusion: a differential gene expression signature in SAT associates with ≥F2 liver fibrosis is explained by a measure of systemic insulin resistance and is not changed by synbiotic treatment. SAT CCGE values are a good predictor of ≥F2 liver fibrosis in NAFLD.

Text
20231113_SupplementaryMaterial - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (1MB)
Text
20231207_Maintext_Tables - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (563kB)
Text
20231113_Figure1 - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (1MB)
Text
20231113_Figure2 - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
20231113_Figure3 - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Image
Figure4 - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
Graphical_Abstract - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
1-s2.0-S0026049523003633-main - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)

Show all 8 downloads.

More information

Accepted/In Press date: 6 December 2023
e-pub ahead of print date: 12 December 2023
Published date: 1 February 2024
Additional Information: Funding Information: JB, PRA, ES, PCC, JKS and CDB were supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre (Grant Number IS-BRC-20004 ). This research was funded in part by the Wellcome Trust [Grant number 206453/Z/17/Z ] to JKS and the European Society for Clinical Nutrition and Metabolism (ESPEN) to PCC. GT is supported in part by grants from the University School of Medicine of Verona , Verona, Italy. SM acknowledges Engineering and Physical Sciences Research Council (EPSRC) funding under the InLightenUs Transformative Healthcare 2050 ( EP/T020997/1 ) and TIQBio EP/V038036/1 programmes. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Keywords: Adipose tissue, Gut microbiome, Liver fibrosis, NAFLD, Synbiotic, Transcriptome

Identifiers

Local EPrints ID: 485308
URI: http://eprints.soton.ac.uk/id/eprint/485308
ISSN: 0026-0495
PURE UUID: e84b08c7-1402-46bd-bc93-7a6f1a086326
ORCID for Josh Bilson: ORCID iD orcid.org/0000-0003-4665-3886
ORCID for Carolina J. Oquendo: ORCID iD orcid.org/0000-0002-9875-0998
ORCID for James Read: ORCID iD orcid.org/0000-0001-5923-1688
ORCID for Paul R. Afolabi: ORCID iD orcid.org/0000-0002-0553-1578
ORCID for Jenny Lord: ORCID iD orcid.org/0000-0002-0539-9343
ORCID for Sumeet Mahajan: ORCID iD orcid.org/0000-0001-8923-6666
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 04 Dec 2023 17:38
Last modified: 12 Jun 2024 04:05

Export record

Altmetrics

Contributors

Author: Josh Bilson ORCID iD
Author: Carolina J. Oquendo ORCID iD
Author: James Read ORCID iD
Author: Eleonora Scorletti
Author: Paul R. Afolabi ORCID iD
Author: Jenny Lord ORCID iD
Author: Laure B. Bindels
Author: Giovanni Targher
Author: Sumeet Mahajan ORCID iD
Author: Diana Baralle ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×