Transcriptional response to enoxolone treatment in larval zebrafish

Using the LipoGlo reporter, in which NanoLuciferase is fused to the endogenous apoBb.1 locus, we performed a whole-animal phenotypic drug screen in larval zebrafish and identified enoxolone (18-beta-glycyrrhetinic acid), a triterpenoid derived from licorice root, as a B-lp-lowering compound. To define the transcriptional pathways underlying this effect, we treated 3 days post fertilization LipoGlo-expressing larvae with 8 uM enoxolone or vehicle and collected whole-animal RNA after 4, 8, 12, 16, or 24 hours of treatment.

Enoxolone induced a transcriptional response detectable by 4 hours that broadened with treatment duration. The early response was enriched for cholesterol and isoprenoid biosynthesis, lipid transport, and coenzyme A metabolism, whereas the late response was enriched for carbohydrate metabolism and signaling pathways. The cholesterol sensor insig1 was upregulated at every duration examined.