The present data show a decrease of ANGPTL-4 levels in children and adolescents with obesity and, for the first time in pediatric subjects, demonstrates a negative correlation between ANGPTL-4 and the main markers of obesity (body weight, BMI, waist circumference, HOMA index, insulin, leptin, and TG). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.