PRF1 and obesity due to melanocortin 4 receptor deficiency: 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.