Obesity Leaves a Molecular 'Memory' in Immune Cells, Study Finds

A 10-year study in EMBO Reports found obesity may leave a lasting imprint on the immune system, keeping some health risks elevated for years after weight loss. The European team, led by Professor Claudio Mauro at the University of Birmingham and backed by the NIHR Biomedical Research Centre: Birmingham, found that helper T cells (CD4+ lymphocytes) retain signs of past obesity long after weight is reduced.

The team focused on DNA methylation, in which chemical tags attach to DNA and switch genes on or off. These tags may persist 5 to 10 years after successful weight loss, affecting autophagy (cells clearing their own waste) and immune senescence (ageing of the immune system). This 'memory' may explain why weight loss does not always lower the risk of obesity-related diseases, including type 2 diabetes and some cancers.

Researchers analysed blood, and in some cases fat tissue, from several groups: obesity patients on weight-loss injections; patients with Alstrom Syndrome, a rare genetic disorder causing early-onset childhood obesity, plus matched healthy pairs; participants after a 10-week exercise programme; and normal-weight or obesity patients having hip or knee replacement for osteoarthritis. They also studied high-fat-diet mice and blood from healthy volunteers.

Mauro said short-term weight loss may not immediately cut the risk of some obesity-related conditions, and fading the 'obesity memory' needs sustained weight management for five to ten years, though this needs further study. He noted repurposing SGLT2 inhibitor drugs as a potential therapy, since they have shown promise reducing inflammation and clearing senescent cells in obesity. Senior author Dr Belinda Nedjai of Queen Mary University London said obesity is linked to durable epigenetic changes that influence immune cell behaviour, and that the immune system appears to retain a molecular record of past metabolic exposures.

The study was carried out through the NIHR Biomedical Research Centre: Birmingham, which supports research aimed at improving outcomes for people living with multiple long-term conditions.