With a significant reduction in Body Fat (although not in BMI or Waist Circumference), an increase in the adiponectin levels, a reduction in the circulating insulin levels and in diastolic blood pressure, and a trend towards a reduction of circulating leptin and glucose levels and HOMA-IR, our findings corroborate the hypothesis that lifestyle interventions could reduce overweight-/obesity-associated systemic inflammation and dysmetabolism. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.