Understanding Obesity’s Long-Lasting Effects

Overcoming obesity is often a tough journey. For many, even after shedding pounds, there’s a continuous battle to stop the weight from creeping back.

The relapse into obesity is surprisingly common, and it seems to be more intricate than just a lack of willpower. Studies indicate that fat cells maintain a ‘memory’ of obesity, lingering long after someone has lost weight, which might complicate their efforts to stay slim.

Interestingly, it extends beyond fat cells. A recent study, spanning a decade, shows that certain immune cells also remember the state of obesity.

This memory could elevate the risk of obesity-related health issues, persisting for up to a decade post-weight loss, according to the study.

The underlying process involves DNA methylation, which is a natural biological occurrence. Here, methyl groups attach to DNA molecules, adjusting gene expression without altering the DNA sequence itself.

In individuals who have recently lost weight, certain modifications to the DNA within helper T cells are believed to keep the memory of being obese alive, encouraging a state of dysregulation and inflammation that can last for years, despite weight loss.

To explore this further, researchers looked at immune cells from various groups of subjects. These included samples from patients with obesity who either engaged in regular exercise for ten weeks or received injections of semaglutide. Control groups were also analyzed.

The study even examined samples from individuals with Alström syndrome, a rare genetic disorder often linked to childhood obesity, as well as healthy matched controls.

The researchers also delved into how obesity might impact immune function over time, analyzing immune cells from mice on high-fat diets, along with blood samples from human volunteers.

“These findings imply that losing weight in the short term might not immediately decrease the risk of certain obesity-related illnesses, including type 2 diabetes and some cancers,” notes co-lead author Claudio Mauro, an immunologist from the University of Birmingham in the UK.

“Ongoing weight management after losing weight is likely to be necessary for the ‘obesity memory’ to gradually diminish,” Mauro explains.

He suggests that this might require several years—likely anywhere from five to ten years—of sustained weight maintenance to fully counter the impacts of obesity on T cells.

These findings illuminate how the immune system manages memory, according to senior author Belinda Nedjai, a molecular epidemiologist at Queen Mary University, London.

“Our results indicate that obesity brings about lasting epigenetic changes affecting how immune cells operate,” Nedjai states.

“This suggests the immune system keeps a molecular record of previous metabolic states, potentially influencing long-term risks for disease and recovery outcomes.”

Research shows that in those with obesity, helper T cells ‘remember’ their state, facilitating weight regain. Yet the exact mechanism behind this has remained elusive.

This recent study identifies two critical cellular functions through which obesity-linked methylation affects helper T cells: autophagy, which is the body’s way of clearing and recycling cell waste, and immune senescence, or the aging of immune cells.

It appears that DNA methylation linked to obesity impacts both of these processes, offering valuable insight into relapse prevalence, says co-author and immunologist Andy Hogan from Maynooth University, Ireland.

“Obesity is a chronic condition, often progressive and relapsing, and our findings deepen the understanding of the molecular drivers behind this risk, emphasizing the hurdles faced by people with obesity in managing their weight effectively,” he remarks.

This research could pave the way for targeted treatments that, combined with other strategies, mitigate the effects of obesity on T cells.

“Our study highlights potential therapeutic avenues to expedite this healing process, like repurposing drugs such as SGLT2 inhibitors, known for their efficacy in reducing inflammation and promoting the immune clearance of senescent cells in cases of obesity,” Mauro adds.

The findings of this study have been published in EMBO Reports.