Thus, the present study aimed to study the association of circulating levels of BDNF, SPARC, FGF-21, and GDF-15 with BMI, the alterations of these four cytokines after 1 year of anti-obesity treatments (lifestyle modification plus pharmacotherapy or bariatric/metabolic surgery), and their association with weight loss at 1 year after obesity therapy. This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.