Grna knockout resists HFD-induced obesity and leads to impaired liver development in zebrafish

Progranulin (PGRN) is a cysteine-rich secreted protein that is expressed in epithelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties and is involved in early embryogenesis and tissue remodelling, acting as an anti-inflammatory molecule. Recently, PGRN was recognized as an adipokine related to obesity and insulin resistance, revealing its metabolic function. In zebrafish, the homologous gene most similar to the human PGRN gene is grna (granulin a). In this study, we used previously obtained grna knockout (KO) zebrafish to investigate the role of grna in obesity resistance and liver development. To explore the role of grna in obesity, grna^-/- zebrafish and wild-type (WT) zebrafish were fed a high-fat diet (HFD) for 2 months. These results indicated that grna^-/- zebrafish were more resistant to HFD-induced obesity than were WT zebrafish. Compared with WT zebrafish, grna^-/- zebrafish presented less visceral fat, abdominal fat, and hepatic fat. In addition, grna^-/- HFD-fed zebrafish presented more severe hepatic vascular fibrosis than WT HFD-fed zebrafish did. During the development of juvenile zebrafish, grna^-/- zebrafish have smaller livers than WT zebrafish do. In conclusion, our findings suggest that grna plays an important role in regulating obesity susceptibility and liver development in zebrafish.