| First Author | Zhao W | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 7 | Pages | 104544 |
| PubMed ID | 35747386 | Mgi Jnum | J:341509 |
| Mgi Id | MGI:7293897 | Doi | 10.1016/j.isci.2022.104544 |
| Citation | Zhao W, et al. (2022) Murine double minute 2 aggravates adipose tissue dysfunction through ubiquitin-mediated six-transmembrane epithelial antigen of prostate 4 degradation. iScience 25(7):104544 |
| abstractText | Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. Mdm2 adipocyte-specific knock-in (Mdm2-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in Mdm2-AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of Mdm2-AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis. |
