PUBLICATION

A zebrafish pparγ gene deletion reveals a protein kinase network associated with defective lipid metabolism

Authors
Zhao, Y., Castro, L.F.C., Monroig, Ó., Cao, X., Sun, Y., Gao, J.
ID
ZDB-PUB-220316-10
Date
2022
Source
Functional & integrative genomics   22(4): 435-450 (Journal)
Registered Authors
Sun, Yonghua
Keywords
Defective lipid metabolism, Kinase, Phosphorylation, Pparγ, Zebrafish
MeSH Terms
  • Adipogenesis
  • Animals
  • Female
  • Gene Deletion
  • Lipid Metabolism*/genetics
  • Male
  • PPAR gamma*/genetics
  • PPAR gamma*/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
35290539 Full text @ Funct. Integr. Genomics
Abstract
Peroxisome proliferator-activated receptor γ (Pparγ) is a master regulator of adipogenesis. Chronic pathologies such as obesity, cardiovascular diseases, and diabetes involve the dysfunction of this transcription factor. Here, we generated a zebrafish mutant in pparγ (KO) with CRISPR/Cas9 technology and revealed its regulatory network. We uncovered the hepatic phenotypes of these male and female KO, and then the male wild-type zebrafish (WT) and KO were fed with a high-fat (HF) or standard diet (SD). We next conducted an integrated analyze of the proteomics and phosphoproteomics profiles. Compared with WT, the KO showed remarkable hyalinization and congestion lesions in the liver of males. Strikingly, pparγ deletion protected against the influence of high-fat diet feeding on lipid deposition in zebrafish. Some protein kinases critical for lipid metabolism, including serine/threonine-protein kinase TOR (mTOR), ribosomal protein S6 kinase (Rps6kb1b), and mitogen-activated protein kinase 14A (Mapk14a), were identified to be highly phosphorylated in KO based on differential proteome and phosphoproteome analysis. Our study supplies a pparγ deletion animal model and provides a comprehensive description of pparγ-induced expression level alterations of proteins and their phosphorylation, which are vital to understand the defective lipid metabolism risks posed to human health.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes