| Title: |
Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes |
| Authors: |
Seyres, D; Cabassi, A; Lambourne, JJ; Burden, F; Farrow, S; McKinney, H; Batista, J; Kempster, C; Pietzner, M; Slingsby, O; Thong, HC; Quinn, PA; Stefanucci, L; Sims, MC; Rehnstrom, K; Adams, CL; Frary, A; Erguener, B; Kreuzhuber, R; Mocciaro, G; D'Amore, S; Koulman, A; Grassi, L; Griffin, JL; Ng, LL; Park, A; Savage, DB; Langenberg, C; Bock, C; Downes, K; Wareham, NJ; Allison, M; Vacca, M; Kirk, PDW; Frontini, M |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2022 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Epigenetics; Metabolites; Lipids; Multi-omics; Obesity; Lipodystrophy; Bariatric surgery; Classification; Innate immune cells; Cardiometabolic syndrome |
| Description: |
Background This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. Methods/results We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. Conclusions We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
CLINICAL EPIGENETICS; ARTN 39; https://qmro.qmul.ac.uk/xmlui/handle/123456789/103576 |
| DOI: |
10.1186/s13148-022-01257-z |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/103576; https://doi.org/10.1186/s13148-022-01257-z |
| Rights: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. ; © The Author(s) 2022. |
| Accession Number: |
edsbas.CB073783 |
| Database: |
BASE |