During exercise, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) mediates the release of METRNL from skeletal muscle into the blood, which plays an important role in browning and insulin sensitization of WAT via regulation of macrophage activity, thus suggesting that METRNL may help mediate exercise-induced protection against metabolic disorders [22]. This evidence concerns the gene INS and metabolic disease.