Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of a...

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Autores principales:	Aisling B. Heeran, Jessica McCready, Margaret R. Dunne, Noel E. Donlon, Timothy S. Nugent, Anshul Bhardwaj, Kathleen A. J. Mitchelson, Amy M. Buckley, Narayanasamy Ravi, Helen M. Roche, John V. Reynolds, Niamh Lynam-Lennon, Jacintha O’Sullivan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adipose tissue immune mediators immune-metabolic signature metabolism oesophageal cancer Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4b17fa7c7aa34e3fb57f33a4372a340f
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spelling	oai:doaj.org-article:4b17fa7c7aa34e3fb57f33a4372a340f2021-11-25T18:20:47ZOpposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction10.3390/metabo111107682218-1989https://doaj.org/article/4b17fa7c7aa34e3fb57f33a4372a340f2021-11-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/768https://doaj.org/toc/2218-1989Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.Aisling B. HeeranJessica McCreadyMargaret R. DunneNoel E. DonlonTimothy S. NugentAnshul BhardwajKathleen A. J. MitchelsonAmy M. BuckleyNarayanasamy RaviHelen M. RocheJohn V. ReynoldsNiamh Lynam-LennonJacintha O’SullivanMDPI AGarticleadipose tissueimmune mediatorsimmune-metabolic signaturemetabolismoesophageal cancerMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 768, p 768 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adipose tissue immune mediators immune-metabolic signature metabolism oesophageal cancer Microbiology QR1-502
spellingShingle	adipose tissue immune mediators immune-metabolic signature metabolism oesophageal cancer Microbiology QR1-502 Aisling B. Heeran Jessica McCready Margaret R. Dunne Noel E. Donlon Timothy S. Nugent Anshul Bhardwaj Kathleen A. J. Mitchelson Amy M. Buckley Narayanasamy Ravi Helen M. Roche John V. Reynolds Niamh Lynam-Lennon Jacintha O’Sullivan Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
description	Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.
format	article
author	Aisling B. Heeran Jessica McCready Margaret R. Dunne Noel E. Donlon Timothy S. Nugent Anshul Bhardwaj Kathleen A. J. Mitchelson Amy M. Buckley Narayanasamy Ravi Helen M. Roche John V. Reynolds Niamh Lynam-Lennon Jacintha O’Sullivan
author_facet	Aisling B. Heeran Jessica McCready Margaret R. Dunne Noel E. Donlon Timothy S. Nugent Anshul Bhardwaj Kathleen A. J. Mitchelson Amy M. Buckley Narayanasamy Ravi Helen M. Roche John V. Reynolds Niamh Lynam-Lennon Jacintha O’Sullivan
author_sort	Aisling B. Heeran
title	Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
title_short	Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
title_full	Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
title_fullStr	Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
title_full_unstemmed	Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction
title_sort	opposing immune-metabolic signature in visceral versus subcutaneous adipose tissue in patients with adenocarcinoma of the oesophagus and the oesophagogastric junction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4b17fa7c7aa34e3fb57f33a4372a340f
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Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction

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