PUBLICATION

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

Authors
Jiang, S., Xu, M., Wu, Y., Liu, Z., Zhao, Y., Zhu, J.
ID
ZDB-PUB-260129-50
Date
2026
Source
Fish physiology and biochemistry   52: 22 (Journal)
Registered Authors
Keywords
grna, CRISPR/Cas9, Liver development, Obesity resistance, Zebrafish
MeSH Terms
  • Animals
  • Diet, High-Fat*/adverse effects
  • Gene Knockout Techniques
  • Liver*/growth & development
  • Obesity*/etiology
  • Obesity*/genetics
  • Progranulins*/genetics
  • Progranulins*/metabolism
  • Zebrafish*/genetics
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
41604044 Full text @ Fish Physiol. Biochem.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping