Interrupting T cell memory ameliorates exaggerated metabolic

Weight cycling has been demonstrated, in humans and animal models, to increase cardiometabolic disease and disrupt glucose homeostasis. Obesity itself — and weight cycling — causes adipose tissue inflammation and metabolic dysfunction. Studies show that even after weight loss, increased numbers of lipid associated macrophages and memory T cells persist in adipose tissue and become more inflammatory upon weight regain. This suggests that the immune system retains an obesogenic memory, which may contribute to the elevated inflammation and metabolic dysfunction associated with weight cycling. Here, we show that blocking the CD70-CD27 axis, critical for formation of immunological memory, decreases the number of memory T cells and T cell clonality within adipose tissue after weight loss and weight cycling. Furthermore, while CD70-/- mice have similar metabolic responses as wildtype mice to stable obesity, they are protected from the worsened glucose tolerance associated with weight cycling. Our data are the first to target metabolic consequences of weight cycling through an immunomodulatory mechanism. We propose a new avenue of therapeutic intervention targeting memory T cells to minimize the adverse consequences of weight cycling. These findings are timely given the increasing use of weight loss drugs, which may lead to more instances of human weight cycling.