For irisin, the indirect effects via HOMA‐IR were significant for obesity (β = 0.020, 95% CI [0.008, 0.040]), abdominal obesity (β = 0.051, 95% CI [0.029, 0.074]) and sarcopenic obesity (β = 0.007, 95% CI [0.001, 0.020]), while the direct effects of irisin were not significant. This evidence concerns the gene FNDC5 and obesity due to melanocortin 4 receptor deficiency.