The inter-organ cross-talking endocrine axis from hepatic FGF21 to adipocyte FGFR1-KLB is a stress-responsive pathway leading to the correction of deranged glucose, lipid and energy metabolism that benefit the organism during conditions of stress-induced pathologies such as obesity, diabetes, fatty liver diseases, malignant transformation and insults from toxins and infection [13,17-20]. The gene discussed is KLB; the disease is obesity due to melanocortin 4 receptor deficiency.