A study found that even after returning to a normal weight, the ‘obesity memory’ etched into immune cells persists, and during this period, the risk of obesity-related diseases such as type 2 diabetes·cancer remains high. Provided by Getty Images Bank
The ‘memory of obesity’ etched into immune cells is not easily erased, even after returning to a normal weight. A new study has found that epigenetic marks left on the DNA of immune cells from experiencing obesity can increase the risk of related diseases, such as type 2 diabetes·cancer, for several years.
A European joint research team led by Professor Claudio Mauro of the University of Birmingham in the UK revealed that helper T cells retain a long-term memory of obesity, publishing their findings in the international journal ‘EMBO Reports’ on the 27th (local time). Helper T cells are a type of T cell belonging to the lymphatic immune system that coordinates the activity of other immune cells.
The research team analyzed the effects of obesity by collecting immune cells from four groups. The subjects of the study included blood from obese patients who received weight-loss injections; blood from patients with Alström syndrome, a rare genetic disorder characterized by early-onset childhood obesity, and from a normal control group; blood and adipose tissue from participants in a 10-week exercise program; and blood and adipose tissue from normal-weight and obese patients who underwent total hip or knee replacement for osteoarthritis. Blood from a mouse model fed a high-fat diet and from healthy adult volunteers was also additionally analyzed.
As a result, it was found that chemical marks attach to specific areas of immune cell DNA in a state of obesity. These marks do not change the gene sequence itself but block certain genes from being read. The problem is that even after returning to a normal weight, these marks remain for 5 to 10 years, causing the immune cells to continue functioning incorrectly.
This ‘obesity memory’ remaining in helper T cells disrupts immune function through two pathways. First, it suppresses ‘autophagy,’ the process by which cells break down and remove their own waste. When this cleaning function deteriorates, damaged cells and protein debris accumulate, causing chronic inflammation and increasing the risk of cancer and metabolic diseases. It also accelerates ‘immune aging.’ A prematurely declining immune system weakens the defense against infections and cancer cells.
The research team analyzed that because the damage to these two pathways persists for years even after returning to a normal weight, the risk of obesity-related diseases also remains high for just as long.
The team plans to develop targeted therapies to restore normal immune functions suppressed by these DNA marks. This could be a therapy used alongside existing weight loss treatments to lower the risk of obesity-related diseases like metabolic disorders and cancer. SGLT2 inhibitors, a treatment for type 2 diabetes, are also being noted as potential candidates, as they have been shown to reduce inflammation in obese patients and promote the immune-mediated removal of aging cells.
Professor Mauro stated, “Short-term weight loss alone does not immediately lower the risk of obesity-related diseases such as type 2 diabetes or some cancers. It appears that 5 to 10 years of sustained weight management are needed for the ‘obesity memory’ to gradually fade and to fully reverse the effects of obesity on T cells.”
Professor Andy Hogan of Maynooth University, Ireland, explained, “Obesity is a chronic, progressive, and relapsing disease. This study reveals the molecular mechanisms that contribute to the risk of relapse and scientifically supports the challenges that people with obesity face in managing their weight.”
doi.org/10.1038/s44319-026-00765-w
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