Here, in a large cohort of young patients affected by severe obesity we investigated the effects of a 4-week program consisting in the association of a Hypocaloric diet plus Physical exercise evaluating, in association with the genetic background, the correlation between circulating levels of adiponectin and anthropometric and biochemical parameters at baseline; then, we looked at the variations in biochemical parameters (Δ values) at the end of the HPP with a particular focus on adiponectin. This evidence concerns the gene ADIPOQ and obesity due to melanocortin 4 receptor deficiency.