In the present study, we only found a modest up-regulation of atgl in the adipose tissue of fish of strain 1, but this up-regulation occurred in association with the up-regulation of sirt6. Fat-specific Sirt6 KO mice promoted high-fat-diet induced obesity by impairing ATGL expression inhibiting the lipolytic activity. This evidence concerns the gene PNPLA2 and obesity due to melanocortin 4 receptor deficiency.