Al-Daghri et al[32] reported that circulating irisin level was negatively correlated with HOMA-IR in a cross-sectional study of girls aged 12.9 ± 3.2 years-old, suggesting that irisin secretion at an early age might delay the onset of obesity, insulin resistance and T2DM. Here, FNDC5 is linked to obesity due to melanocortin 4 receptor deficiency.