PUBLICATION
Nkx1.2 deletion decreases fat production in zebrafish
- Authors
- Wang, X., Li, X., Wang, Y., Ren, Z., Du, X., Gao, J., Ji, G., Liu, Z.
- ID
- ZDB-PUB-240527-12
- Date
- 2024
- Source
- Obesity (Silver Spring, Md.) 32(7): 1315-1328 (Journal)
- Registered Authors
- Liu, Zhenhui
- Keywords
- none
- MeSH Terms
-
- Homeobox Protein Nkx-2.2
- Mice
- Promoter Regions, Genetic
- Signal Transduction
- Lipid Metabolism/genetics
- Adipocytes/metabolism
- Adipogenesis/genetics
- 3T3-L1 Cells*
- CRISPR-Cas Systems
- Zebrafish*
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Homeodomain Proteins*/genetics
- Homeodomain Proteins*/metabolism
- Animals
- Larva/metabolism
- Cell Differentiation
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Lipid Droplets/metabolism
- PubMed
- 38798028 Full text @ Obesity (Silver Spring)
Citation
Wang, X., Li, X., Wang, Y., Ren, Z., Du, X., Gao, J., Ji, G., Liu, Z. (2024) Nkx1.2 deletion decreases fat production in zebrafish. Obesity (Silver Spring, Md.). 32(7):1315-1328.
Abstract
Objective This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production.
Methods Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment.
Results Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells.
Conclusions Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping