We provide evidence of the existence of the cardiometabolically healthy obesity phenotype and highlight the potential of adipokines such as leptin, adiponectin, IL-18, and chemerin; the inflammatory marker hs-CRP; and gut dysbiosis, as indicators of the evolution from the cardiometabolically healthy to the cardiometabolically abnormal phenotype within this population. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.