Fruhbeck et al. showed that a reduced adiponectin/leptin ratio was associated with higher levels of the inflammation markers CRP and serum amyloid A (SAA), demonstrating that in severe obesity and MetS, adipose tissue dysfunction characterized by the adiponectin/leptin ratio leads to an increase in pro-inflammatory factors as potential mediators in their etiopathogenesis [39]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.