White blood cells see their DNA tagged with obesity, and can lead to ongoing risk of related illness long after weight loss
People who live with obesity are ‘tagging’ a memory of being overweight on a key part of the immune system - leaving people with ongoing risk of obesity-related conditions years after losing weight, according to a 10 year-long study published in EMBO Reports.
A European research team led by Professor Claudio Mauro from the University of Birmingham supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Birmingham have shown that immune cells known as helper T cells (or CD4+ lymphocytes) carry a long memory of obesity.
Through a process known as DNA methylation, tags or markers attach themselves to DNA in the immune cells. This ‘tagging’ is likely to last between 5-10 years after people successfully lose weight. The resulting impact of the ‘memory’ of obesity in helper T cells could cause dysregulation of some usual activities that the immune system typically does, including cleaning away waste and regulating immune ageing.
The National Institute for Health and Care ResearchThe research team believe that this could leave people who do lose weight to continue to be at risk of obesity-related conditions long after reaching a normal weight.
ongoing weight management following loss will see the ‘obesity memory’ slowly fade
Researchers took immune cells from four groups of people to provide the most detailed picture of the impact of obesity. The study included:
The work additionally studied cells from mice models fed on a high-fat diet, and blood donations from healthy human volunteers. These models were used to help look at the mechanisms within cells that underpin immune dysregulation in obesity.
Professor Claudio Mauro from the Department of Inflammation and Ageing at the University of Birmingham who is co-lead author of the study said: “The findings suggest that short-term weight loss may not immediately reduce the risk of some disease conditions associated with obesity, including type 2 diabetes and some cancers.
“Instead, ongoing weight management following loss will see the ‘obesity memory’ slowly fade. This may take several years of sustained weight loss maintenance, likely 5-10 years, though this requires further study, to fully reverse the effects of obesity on T cells.
“Additionally, our study suggests potential therapeutic opportunities to expedite this process, such as repurposing drugs like SGLT2 inhibitors, which have shown promise in reducing inflammation and promoting immune-mediated clearance of senescent cells in obesity.”
The author team identify two specific pathways through which tagging affects helper T cells.
The memory of obesity is thought to affect autophagy (where cells eat bits of themselves to clean away the waste) and immune senescence (which is ageing of the immune system). The research team will use these findings to help look for targeted treatments that help restore typical immune system functioning that is being inhibited by the DNA tagging. The resulting potential treatments could then be used alongside existing weight loss therapies to reduce the risk of conditions including metabolic diseases and cancer that are exacerbated by obesity.
Dr Belinda Nedjai from the Wolfson Institute of Population Health at Queen Mary University London and senior author of the paper said: “Our findings show that obesity is associated with durable epigenetic modifications that influence immune cell behaviour. This suggests that the immune system retains a molecular record of past metabolic exposures, which may have implications for long-term disease risk and recovery.”
Professor Andy Hogan from the Kathleen Lonsdale Institute for Human Health Research at Maynooth University Ireland said: “We know obesity is a chronic progressive and relapsing disease and our findings provide further understanding of exactly what are the molecular mechanisms potentially driving the risk of relapsing and highlight the challenges facing people living with obesity to successfully manage their weight.”
The study was delivered through the NIHR Biomedical Research Centre: Birmingham, which supports research focused on improving outcomes for people with multiple long‑term conditions.
For media enquiries please contact Tim Mayo, Press Office, University of Birmingham, tel: +44 (0)7815 607 157.
The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, educators and more than 40,000 students from over 150 countries.
England’s first civic university, the University of Birmingham is proud to be rooted in of one of the most dynamic and diverse cities in the country. A member of the Russell Group and a founding member of the Universitas 21 global network of research universities, the University of Birmingham has been changing the way the world works for more than a century.
The University of Birmingham is a founding member of Birmingham Health Partners (BHP), a strategic alliance which transcends organisational boundaries to rapidly translate healthcare research findings into new diagnostics, drugs and devices for patients. Birmingham Health Partners is a strategic alliance between nine organisations who collaborate to bring healthcare innovations through to clinical application:
The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:
NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.
The NIHR Biomedical Research Centre: Birmingham (BRC) is part of the NIHR and hosted by University Hospitals Birmingham NHS Foundation Trust (UHBFT) in partnership with the University of Birmingham (UoB). The BRC’s research programme focuses on inflammation and the diagnosis, prevention and treatment of its associated long-term illnesses.
Professor of Metabolism and Inflammation
Professor Claudio Mauro, Professor of Metabolism and Inflammation and British Heart Foundation Senior Basic Science Research Fellow, University of Birmingham.
