PUBLICATION
Targeting Seipin to Alleviate Hepatic Steatosis in Zebrafish (Danio Rerio)
- Authors
- Li, W., Shen, Y., Zhao, Z., Li, B., Wen, S., Zhan, R., Ai, Q.
- ID
- ZDB-PUB-250813-17
- Date
- 2025
- Source
- Advanced science (Weinheim, Baden-Wurttemberg, Germany) : e07777e07777 (Journal)
- Registered Authors
- Keywords
- Hepatic steatosis, Phosphatidylcholine, Seipin, Zebrafish
- MeSH Terms
-
- Animals
- Diet, High-Fat/adverse effects
- Disease Models, Animal
- Fatty Liver*/genetics
- Fatty Liver*/metabolism
- GTP-Binding Protein gamma Subunits*/genetics
- GTP-Binding Protein gamma Subunits*/metabolism
- Lipid Metabolism/genetics
- Liver/metabolism
- Mice
- Perilipin-2/genetics
- Perilipin-2/metabolism
- Triglycerides/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40799131 Full text @ Adv Sci (Weinh)
Citation
Li, W., Shen, Y., Zhao, Z., Li, B., Wen, S., Zhan, R., Ai, Q. (2025) Targeting Seipin to Alleviate Hepatic Steatosis in Zebrafish (Danio Rerio). Advanced science (Weinheim, Baden-Wurttemberg, Germany). :e07777e07777.
Abstract
Loss of Seipin causes the absence of whole-body adipose but abnormal liver lipid deposition in patients, and liver expression of Seipin is decreased in mice fed a high-fat diet (HFD). However, the underlying mechanism of Seipin-regulated liver lipid metabolism remains mysterious. Here, experiments show that over-expression of Seipin down-regulates HFD-induced liver triglyceride (TG) accumulation and promotes zebrafish growth. Real-time PCR and immunoblotting suggest that Seipin interacts with Plin2 through its second transmembrane domain to inhibit the expression of Plin2 by promoting Plin2 ubiquitination, thereby ameliorating lipid accumulation. Co-immunoprecipitation (CoIP) experiments and Biomolecular fluorescence complementation (BiFC) analysis reveal a close interaction between Seipin and phosphatidylcholine (PC) synthesis enzyme CCTα and CHPT in zebrafish and mice. Thus, Seipin may participate in PC synthesis and increase cellular PC levels. Elevated PC levels subsequently suppress Plin2 expression. Meanwhile, CCTα, the rate-limiting enzyme of the PC synthesis pathway, exhibited a unique regulatory role on Plin2 expression as a potential transcription factor. It is proposed that Seipin balances TG homeostasis, PC synthesis, and Plin2 expression to alleviate hepatic steatosis, providing a promising target for fatty liver disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping