First, hepatic Rspo3 expression was shown to be enhanced and to converge around central veins in response to feeding as compared to the fasting state (i.e., spatiotemporal characteristics of Rspo3), while being attenuated in obesity, reflecting the physiological and pathophysiological significance of Rspo3. This evidence concerns the gene RSPO3 and obesity due to melanocortin 4 receptor deficiency.