CD4+ T cells memorize obesity and promote weight regain

Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown. In this study, we report that immune cells, especially CD4+ T cells, mediate the 'memory' of previous obese status. In a weight gain-loss-regain model, we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain. This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice. Surprisingly, such obesity memory was abrogated by dexamethasone treatment, whereas immunodeficient Rag1^-/- and H2A^-/- mice failed to establish such memory. Rag1^-/- mice repossessed the obesity memory when immune cells or CD4+ T cells isolated from previously obese mice were transferred. Furthermore, depletion of CD4+ T cells led to obesity memory ablation. Taken together, we conclude that CD4+ T cells mediate obesity memory and promote weight regain.