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
Bilson, Josh
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Oquendo, Carolina J.
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Read, James
ab0a5309-095b-4db1-ab90-913f2847c81e
Scorletti, Eleonora
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Afolabi, Paul R.
757e7f01-664c-493e-bc51-c6a2c933dc22
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Bindels, Laure B.
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Targher, Giovanni
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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
1 February 2024
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).
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.
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Accepted/In Press date: 6 December 2023
e-pub ahead of print date: 12 December 2023
Published date: 1 February 2024
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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
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Date deposited: 04 Dec 2023 17:38
Last modified: 24 Apr 2024 04:05
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