Defeating obesity is rarely easy, and even successful weight loss is followed by a struggle to prevent the weight from returning. Now, a decade-long study reveals that certain immune cells carry a persistent 'memory' of obesity, potentially undermining efforts to avoid regaining weight and preserving an elevated risk of obesity-related illness for up to 10 years after slimming down.
Researchers from the University of Birmingham and Queen Mary University London found that helper T cells retain a cellular memory of obesity through DNA methylation-a process where methyl groups latch onto DNA, altering gene activity without changing the DNA sequence. This promotes a dysregulated, pro-inflammatory condition that can endure for years despite reductions in body weight.
"Short-term weight loss may not immediately reduce the risk of some disease conditions associated with obesity, including type 2 diabetes and some cancers," says co-lead author Claudio Mauro, an immunologist at the University of Birmingham. "Instead, ongoing weight management following loss will see the 'obesity memory' slowly fade. This may take several years of sustained weight loss maintenance, likely five to 10 years, to fully reverse the effects of obesity on T cells."
The study identifies two key pathways for obesity-related methylation: autophagy, the natural removal of cellular waste, and immune senescence, or aging of cells in the immune system. The findings suggest potential therapeutic opportunities using drugs like SGLT2 inhibitors, which have shown promise in reducing inflammation and promoting immune-mediated clearance of senescent cells in obesity.