Despite this moderate yet significant basal cytokines production, iNKT cells from individuals with obesity display profound functional defect, characterized by a hypo-responsiveness to ex vivo stimulation with PMA/ionomycin, as demonstrated by the marked reduction in Th1 cytokines (IFN-γ, TNF-α) and perforin production. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.