On the other hand, several pivotal costimulatory receptors on T cells such as 4-1BB and CD28 are reported to be implicated in obesity-induced adipose tissue inflammation and metabolic disorders, as evidenced by the fact that 4-1BB or CD28 deficiency in mice improves related metabolic parameters and reduces T cell infiltration in VAT (64, 65). The gene discussed is TNFRSF9; the disease is obesity due to melanocortin 4 receptor deficiency.