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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 |
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| ISSN: | 1469-3178 |
| Published: |
Springer Nature
2026
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71815 |
| 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 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. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
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. |