Our main findings suggest that: (1) Significant differences in irisin concentrations were observed over time during an acute bout of HIIT, (2) significant differences in percent change in irisin concentrations were observed between exercise conditions, (3) youth with a healthy weight elicited an increase in irisin concentration during HIIT session, whereas those living as overweight or with obesity did not have a significant change in irisin during exercise, and (4) fat mass and LDL cholesterol were negatively correlated with irisin release. The gene discussed is FNDC5; the disease is obesity due to melanocortin 4 receptor deficiency.