Vitamin D Receptor regulation of hepatic energy metabolism in zebrafish

Vitamin D deficiency and mutations in Vitamin D Receptor (VDR) are associated with liver disease and obesity, but the functions of vitamin D signaling in metabolism are poorly understood. Though vitamin D signaling is best known for its functions in mineral homeostasis and skeleton calcification in terrestrial vertebrates, this is unlikely to be the evolutionary function of vitamin D signaling. We utilize tissue-specific genetic modulation of Vdr signaling to investigate the function of the vitamin D endocrine system in zebrafish. We find that hepatocyte Vdr regulates organismal response to nutritional cues and coordinates hepatic and organismal energy metabolism by balancing energy storage and tissue growth. Overall design: Comparative gene expression profiling analysis of RNA-seq data following hepatocyte-specific Vdr modulation in larval and adult zebrafish. fabp10a:dn-vdra and fabp10a:ca-vdra transgenes were used to achieve hepatocyte Vdr impairment or hyperactivation, respectively. Larval experiments were performed on sorted hepatocytes at 96 hours post fertilization (hpf) and reflect approximately 35 pooled fish per sample. Adult experiments were performed on dissected male liver collected at 4.5 months post fertilization (mpf) and are composed of 3 livers per sample. wild-type controls are included for each experiment. For larval fabp10a:dn-vdra, N = 4 wt, 4 dn-vdra. For fabp10a:ca-vdra, N = 4 wt, 3 ca-vdra. For adult fabp10a:dn-vdra, N = 4 wt, 4 dn-vdra.