PUBLICATION
Compromised COPII vesicle trafficking leads to glycogenic hepatopathy in zebrafish
- Authors
- Yang, Y., Zhang, X., Zhao, Q., Zhang, J., Lou, X.
- ID
- ZDB-PUB-240814-11
- Date
- 2024
- Source
- Disease models & mechanisms 17(9): (Journal)
- Registered Authors
- Lou, Xin, Yang, Yuxi, Zhao, Qingshun
- Keywords
- COPII vesicle, Glycogenic hepatopathy, Liver disease, Thyroid hormone, Zebrafish
- Datasets
- GEO:GSE248098
- MeSH Terms
-
- Activating Transcription Factor 4/metabolism
- Unfolded Protein Response/drug effects
- Eukaryotic Initiation Factor-2/metabolism
- Thyroid Hormones/metabolism
- Glycogen/metabolism
- Fatty Liver/metabolism
- Fatty Liver/pathology
- Signal Transduction
- Animals
- Liver Diseases/metabolism
- Liver Diseases/pathology
- Liver*/metabolism
- Liver*/pathology
- COP-Coated Vesicles*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Protein Transport/drug effects
- Larva/metabolism
- Hypothyroidism/metabolism
- Hypothyroidism/pathology
- Zebrafish*/metabolism
- PubMed
- 39139065 Full text @ Dis. Model. Mech.
Citation
Yang, Y., Zhang, X., Zhao, Q., Zhang, J., Lou, X. (2024) Compromised COPII vesicle trafficking leads to glycogenic hepatopathy in zebrafish. Disease models & mechanisms. 17(9):.
Abstract
Being a vital cellular process, COPII vesicle trafficking has been found plays a crucial role in liver metabolism. However, its functions and the underlying mechanisms in systemic metabolic homeostasis have not been fully understood. Here, with a newly identified gene trap zebrafish line (sec31anju221), we show that compromised COPII vesicle trafficking leads to biphasic abnormal hepatic metabolism. During the larval stage, deficiency of COPII-mediated trafficking leads to activation of unfolded protein reaction (UPR) and the development of hepatic steatosis. By using epistasis analysis, we found eIF2a/ATF4 branch serves as the primary effector for liver steatosis. In adult sec31anju221 fish, the hepatosteatosis was reversed and the phenotype swing to glycogenic hepatopathy. Proteomic profiling and biochemical assay indicate sec31anju221 fish are in a state of hypothyroidism. Moreover, our study showed thyroid hormone treatment alleviates the metabolic defects. This study provides insights into processes of liver diseases associated with vesicle trafficking impairments and has expanded our understanding of the pathological interplay between thyroid and liver.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping