RNA-Sequence of the liver after administration of adenovirus associated with metabolic liver zonation
Metabolic zonation in the liver is broadly defined as spatiotemporal variability in the intra-hepatic distribution of nutrients. R-spondin3 (Rspo3) regulates metabolic features around hepatic central veins. Herein, we demonstrate that altered hepatic metabolic zonation due to Rspo3 contributes to maintaining systemic glucose metabolism and body composition via inter-organ communication mechanism. Hepatic Rspo3 induction in obesity improves obesity-associated features by restoring insulin sensitivity, reversing adipose tissue enlargement and reversing overstimulated adaptive thermogenesis. These remote effects partly consist of neuronal communication via the afferent vagus from the liver. In contrast, hepatic Rspo3 suppression exacerbates diabetes due to insulin resistance and develops fatty liver. Overall design: To examine whether a molecule associated with metabolic liver zonation has an effect on systemic metabolism, we first administer adenoviruses expressing Rspo3 or LacZ (control) into the murine liver. Then, by performing RNA-Sequence analysis, we compare hepatic gene expression of Rspo3-mice with that of LacZ-mice.