PUBLICATION
Depletion of Igfbp7 alleviates zebrafish NAFLD progression through inhibiting hepatic ferroptosis
- Authors
- Wang, Y., Bo, J., Zhao, Z., Han, Y., Zhang, Q., Liu, L.
- ID
- ZDB-PUB-230916-58
- Date
- 2023
- Source
- Life sciences 332: 122086 (Journal)
- Registered Authors
- Zhao, Zhonghua
- Keywords
- Ferritinophagy, Ferroptosis, Igfbp7, NAFLD, Zebrafish NAFLD model
- MeSH Terms
-
- Animals
- Diet, High-Fat
- Ferroptosis*
- Humans
- Insulin-Like Growth Factor Binding Proteins*/genetics
- Liver/metabolism
- Liver Cirrhosis/pathology
- Non-alcoholic Fatty Liver Disease*/metabolism
- Zebrafish
- PubMed
- 37714372 Full text @ Life Sci.
Citation
Wang, Y., Bo, J., Zhao, Z., Han, Y., Zhang, Q., Liu, L. (2023) Depletion of Igfbp7 alleviates zebrafish NAFLD progression through inhibiting hepatic ferroptosis. Life sciences. 332:122086.
Abstract
Aims The global increased expression of Insulin-like growth factor binding protein 7 (IGFBP7) has been detected in non-alcoholic fatty liver disease (NAFLD) patients, however, its roles in NAFLD and the mechanism remain largely unclear. The goal of this study is to investigate the effect and mechanism of Igfbp7 using a zebrafish NAFLD model.
Main methods The igfbp7-/- null zebrafish mutant and the Igfbp7 liver overexpressed (LOE) transgenic zebrafish based on Gal4/UAS system were generated by CRISPR/Cas9 and Tol2 transgenic technique, respectively. The zebrafish NAFLD models in wildtypes, igfbp7-/- mutants and Igfbp7 LOE fishes have been established by high-fat diet feeding. The Igfbp7 dynamic expression and its effects on NAFLD progression have been detected and analyzed in both human NAFLD patients and zebrafish models. And the potential mechanism has been investigated through transcriptome analysis and subsequent detection and verification.
Key findings High Igfbp7 levels in NASH and fibrosis stages have been detected in liver tissues of both human NAFLD patients and zebrafish models. Depletion of Igfbp7 significantly alleviated liver steatosis, inflammation, and fibrosis, whereas liver specific Igfbp7 overexpression dramatically exacerbated liver fibrosis in zebrafish NAFLD model. The hepatic iron deposition, lipid peroxidation products, and ferroptosis-related index were also significantly reduced at the NASH stage in the absence of Igfbp7. Igfbp7 promotes NAFLD progression through regulating ferroptosis, and Ncoa4-mediated ferritinophagy may be the pathway of Igfbp7-regulated ferroptosis.
Significance Igfbp7 is confirmed as an important regulator in NAFLD progression. Depleting Igfbp7 effectively alleviates zebrafish NAFLD progression by inhibiting hepatic ferroptosis, suggesting a novel potential target for NAFLD treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping