Zebrafish leg1a and leg1b double null mutant accumulates lipids in the liver

Zebrafish Leg1a and Leg1b are two homologous proteins sharing high sequence homology. Previous studies have revealed that leg1a and leg1b genes are important for early liver development and Leg1a and Leg1b are liver-produced serum proteins, however, whether they play a physiological role in the zebrafish liver remains unknown. Here, we carry out an analysis of the bulk RNA sequencing (RNA-seq) data and find that lipid metabolic pathways are the most prominently affected biological processes in the leg1a^-/-leg1b^-/- double mutant larvae. Oil-Red-O staining shows a significant accumulation of lipids in the leg1a^-/-leg1b^-/- double mutant larvae and adult livers. Lipidomics analysis reveals that the increased lipids are mainly diacylglycerol (DAG) in the adult liver. Our findings identify the essential role of Leg1 in maintaining the lipid metabolic homeostasis in zebrafish.