Obesity imprints CD4 T cells via DNA methylation, perpetuating immune dysregulation

Children with obesity are highly likely to carry it into adulthood, bringing numerous associated health risks. Even more troubling is the emerging understanding of “obesity memory”, which contributes to the frequent issue of weight regain.

Here, we show that obesity imprints CD4 T cells through DNA methylation, leading to a long-time lag, spanning years, before adaptive immune homeostasis is restored after weight loss. Differential DNA methylation analysis highlighted autophagy and immune senescence as key mechanisms underpinning this memory of obesity in CD4 T cells. Additionally, saturated fatty acids, in particular palmitate, drive epigenetic changes in CD4 T cells, perpetuating this altered state.