Journal article 104 views
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation
Jennifer Niven,
Salih Kucuk 
,
Atrayee Gope,
Michelangelo Certo ,
Fearon C Cassidy ,
Ainhoa Arana Echarri,
Sadaf Ali ,
Efthymios Ladoukakis ,
Sofia Vidali ,
Chiara Macchi,
Sayeda S Amir,
Ronan Bergin ,
Sophie Davies ,
Oliver J Perkin ,
Joanne Smith,
Danilo Cucchi,
Helen Heneghan,
Susanne Wijesinghe,
Benjamin Jenkins,
Shanat Baig ,
Christopher Mahony ,
Chiamaka Chidomere ,
Sovan Sarkar,
Anna Nicolaou ,
Jorge Caamaño ,
Adam Croft,
Edward Davies,
Dylan Thompson,
Donal O’Shea,
Simon W Jones ,
Niharika A Duggal,
Massimiliano Ruscica ,
Maria Makarova,
Nick Jones ,
Gabriela Da Silva Xavier ,
Tarekegn Geberhiwot,
James E Turner,
Andrew E Hogan ,
Belinda Nedjai,
Claudio Mauro
,
Atrayee Gope,
Michelangelo Certo ,
Fearon C Cassidy ,
Ainhoa Arana Echarri,
Sadaf Ali ,
Efthymios Ladoukakis ,
Sofia Vidali ,
Chiara Macchi,
Sayeda S Amir,
Ronan Bergin ,
Sophie Davies ,
Oliver J Perkin ,
Joanne Smith,
Danilo Cucchi,
Helen Heneghan,
Susanne Wijesinghe,
Benjamin Jenkins,
Shanat Baig ,
Christopher Mahony ,
Chiamaka Chidomere ,
Sovan Sarkar,
Anna Nicolaou ,
Jorge Caamaño ,
Adam Croft,
Edward Davies,
Dylan Thompson,
Donal O’Shea,
Simon W Jones ,
Niharika A Duggal,
Massimiliano Ruscica ,
Maria Makarova,
Nick Jones ,
Gabriela Da Silva Xavier ,
Tarekegn Geberhiwot,
James E Turner,
Andrew E Hogan ,
Belinda Nedjai,
Claudio Mauro
EMBO Reports
Swansea University Authors:
Benjamin Jenkins, Nick Jones
-
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DOI (Published version): 10.1038/s44319-026-00765-w
Abstract
Obesity represents a major global healthcare crisis, with childhood obesity rising at an alarming rate. Children with obesity are highly likely to carry it into adulthood, bringing numerous associated health risks. Even more troubling is the emerging understanding of “obesity memory”, which contribu...
| Published in: | EMBO Reports |
|---|---|
| ISSN: | 1469-3178 |
| Published: |
Springer Nature
2026
|
| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71815 |
| first_indexed |
2026-04-28T08:35:40Z |
|---|---|
| last_indexed |
2026-05-14T05:30:14Z |
| id |
cronfa71815 |
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SURis |
| fullrecord |
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C Mauro, SWJ, ND, and MR are supported by the Doctorate Training Network Award HORIZON – MSCA – 2024 – DN 101167421. JN is supported by a University of Birmingham British Heart Foundation Accelerator Award. NJ is supported by the Medical Research Council New Investigator Research Grant MR/ X000095/1. SS is supported by the Medical Research Council Project Grant MR/Z504488/1 and Action Medical Research/LifeArc Grant GN3049. 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2026-05-13T15:12:48.5772880 v2 71815 2026-04-28 DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation 90f7cfd66781feba615436189178a528 Benjamin Jenkins Benjamin Jenkins true false 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 2026-04-28 MEDS Obesity represents a major global healthcare crisis, with childhood obesity rising at an alarming rate. Children with obesity are highly likely to carry it into adulthood, bringing numerous associated health risks. Even more troubling is the emerging understanding of “obesity memory”, which contributes to the frequent issue of weight regain. Here, we show that obesity imprints CD4 T cells through DNA methylation, leading to a long-time lag, spanning years, before adaptive immune homeostasis is restored after weight loss. Differential DNA methylation analysis highlights autophagy and immune senescence as potential key mechanisms underpinning this memory of obesity in CD4 T cells. In addition, particularly palmitate could be a key saturated fatty acid that can contribute to epigenetic alterations in CD4 T cells, potentially perpetuating this altered state. We identify molecular candidates (i.e., Stk26 and Cdkn1c) underpinning key cell functions (autophagy and immune senescence) that could be targeted to promote a return to immune homeostasis alongside weight loss. These findings raise the possibility that targeting such pathways could support the restoration of immune homeostasis alongside weight loss therapies. Journal Article EMBO Reports 0 Springer Nature 1469-3178 27 4 2026 2026-04-27 10.1038/s44319-026-00765-w COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee C Mauro is supported by a Professorial Research Fellowship by the University of Birmingham, the Medical Research Council Project Grant MR/T016736/1, and the British Heart Foundation Basic Science Research Fellowship FS/SBSRF/22/31031. C Mauro, SWJ, ND, and MR are supported by the Doctorate Training Network Award HORIZON – MSCA – 2024 – DN 101167421. JN is supported by a University of Birmingham British Heart Foundation Accelerator Award. NJ is supported by the Medical Research Council New Investigator Research Grant MR/ X000095/1. SS is supported by the Medical Research Council Project Grant MR/Z504488/1 and Action Medical Research/LifeArc Grant GN3049. SWJ is supported by the Medical Research Council Project Grant MR/W026961/1 and Versus Arthritis grants 21530 and 21812. 2026-05-13T15:12:48.5772880 2026-04-28T09:34:58.7823190 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Jennifer Niven 1 Salih Kucuk 0000-0002-0939-8508 2 Atrayee Gope 3 Michelangelo Certo 0000-0002-5568-3465 4 Fearon C Cassidy 0000-0003-2577-9519 5 Ainhoa Arana Echarri 6 Sadaf Ali 0000-0001-6768-5495 7 Efthymios Ladoukakis 0000-0002-4807-1292 8 Sofia Vidali 0000-0002-0789-0849 9 Chiara Macchi 10 Sayeda S Amir 11 Ronan Bergin 0000-0003-4685-7176 12 Sophie Davies 0000-0002-6069-1056 13 Oliver J Perkin 0000-0001-8921-8708 14 Joanne Smith 15 Danilo Cucchi 16 Helen Heneghan 17 Susanne Wijesinghe 18 Benjamin Jenkins 19 Shanat Baig 0000-0003-1625-6839 20 Christopher Mahony 0000-0003-4487-2540 21 Chiamaka Chidomere 0000-0003-3118-4896 22 Sovan Sarkar 23 Anna Nicolaou 0000-0002-1314-413x 24 Jorge Caamaño 0000-0003-3530-7056 25 Adam Croft 26 Edward Davies 27 Dylan Thompson 28 Donal O’Shea 29 Simon W Jones 0000-0001-6785-2310 30 Niharika A Duggal 31 Massimiliano Ruscica 0000-0002-0195-7061 32 Maria Makarova 33 Nick Jones 0000-0003-4846-5117 34 Gabriela Da Silva Xavier 0000-0002-0678-012x 35 Tarekegn Geberhiwot 36 James E Turner 37 Andrew E Hogan 0000-0001-5875-230x 38 Belinda Nedjai 39 Claudio Mauro 0000-0002-3736-0099 40 71815__36720__50d345fa0c3b4fb0b93edc92a0beae38.pdf 71815.VOR.pdf 2026-05-13T15:06:19.9447405 Output 5979344 application/pdf Version of Record true © The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/ |
| title |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
| spellingShingle |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation Benjamin Jenkins Nick Jones |
| title_short |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
| title_full |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
| title_fullStr |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
| title_full_unstemmed |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
| title_sort |
DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation |
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90f7cfd66781feba615436189178a528 0fce0f7ddbdbfeb968f4e2f1e3f86744 |
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90f7cfd66781feba615436189178a528_***_Benjamin Jenkins 0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones |
| author |
Benjamin Jenkins Nick Jones |
| author2 |
Jennifer Niven Salih Kucuk Atrayee Gope Michelangelo Certo Fearon C Cassidy Ainhoa Arana Echarri Sadaf Ali Efthymios Ladoukakis Sofia Vidali Chiara Macchi Sayeda S Amir Ronan Bergin Sophie Davies Oliver J Perkin Joanne Smith Danilo Cucchi Helen Heneghan Susanne Wijesinghe Benjamin Jenkins Shanat Baig Christopher Mahony Chiamaka Chidomere Sovan Sarkar Anna Nicolaou Jorge Caamaño Adam Croft Edward Davies Dylan Thompson Donal O’Shea Simon W Jones Niharika A Duggal Massimiliano Ruscica Maria Makarova Nick Jones Gabriela Da Silva Xavier Tarekegn Geberhiwot James E Turner Andrew E Hogan Belinda Nedjai Claudio Mauro |
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EMBO Reports |
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2026 |
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Swansea University |
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1469-3178 |
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10.1038/s44319-026-00765-w |
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Springer Nature |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science |
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Obesity represents a major global healthcare crisis, with childhood obesity rising at an alarming rate. Children with obesity are highly likely to carry it into adulthood, bringing numerous associated health risks. Even more troubling is the emerging understanding of “obesity memory”, which contributes to the frequent issue of weight regain. Here, we show that obesity imprints CD4 T cells through DNA methylation, leading to a long-time lag, spanning years, before adaptive immune homeostasis is restored after weight loss. Differential DNA methylation analysis highlights autophagy and immune senescence as potential key mechanisms underpinning this memory of obesity in CD4 T cells. In addition, particularly palmitate could be a key saturated fatty acid that can contribute to epigenetic alterations in CD4 T cells, potentially perpetuating this altered state. We identify molecular candidates (i.e., Stk26 and Cdkn1c) underpinning key cell functions (autophagy and immune senescence) that could be targeted to promote a return to immune homeostasis alongside weight loss. These findings raise the possibility that targeting such pathways could support the restoration of immune homeostasis alongside weight loss therapies. |
| published_date |
2026-04-27T06:30:14Z |
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1865140524315312128 |
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11.105529 |