Our present results raise the possibility that reconstitution of hepatic metabolic zonation by Rspo3 induction in obesity, with increased WAT-derived thermogenesis and reversal of overstimulated BAT-derived thermogenesis, may lead to balancing and redistribution of thermogenesis derived from different adipose tissues such as WAT and BAT. The gene discussed is RSPO3; the disease is obesity due to melanocortin 4 receptor deficiency.