T cells with increased responsiveness cause obesity in mice without diet intervention

Abstract

Obesity is a complex multicausal disease that can cause morbidity and mortality, and there is need for improved knowledge on the underlying mechanisms. Using a mouse model of increased Tcell responsiveness, we show that development of obesity can be driven by immune cells. This was confirmed with bone marrow transplantation and adoptive Tcell transfer to several recipient mouse models. Single-cell RNA sequencing and CyTOF analysis showed that the mice display altered composition of circulating Tcells and increased Tcell activation in visceral adipose tissue, suggesting activated Tcells as critical players in the increased fat mass. In this study, we provide evidence that obesity can be driven by immune cell activity and in particular by Tcells, which could have broad implications for prevention and treatment of this condition.