Research
| Title： | A zebrafish ppar gamma gene deletion reveals a protein kinase network associated with defective lipid metabolism |
|---|---|
| First author： | Zhao, Yan; Castro, L. Filipe C.; Monroig, Oscar; Cao, Xiaojuan; Sun, Yonghua; Gao, Jian |
| Journal： | FUNCTIONAL & INTEGRATIVE GENOMICS |
| Years： | 2022 |
| DOI： | 10.1007/s10142-022-00839-7 |
| Abstract： | Peroxisome proliferator-activated receptor gamma (Ppar gamma) 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 ppar gamma (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, ppar gamma 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 ppar gamma deletion animal model and provides a comprehensive description of ppar gamma-induced expression level alterations of proteins and their phosphorylation, which are vital to understand the defective lipid metabolism risks posed to human health. |
