| First Author | Wu YK | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 524 |
| Issue | 1 | Pages | 142-149 |
| PubMed ID | 31982140 | Mgi Jnum | J:292200 |
| Mgi Id | MGI:6447566 | Doi | 10.1016/j.bbrc.2020.01.037 |
| Citation | Wu YK, et al. (2020) Targeting DUSP16/TAK1 signaling alleviates hepatic dyslipidemia and inflammation in high fat diet (HFD)-challenged mice through suppressing JNK MAPK. Biochem Biophys Res Commun 524(1):142-149 |
| abstractText | Nonalcoholic fatty liver disease (NAFLD) is featured by hepatic steatosis, insulin resistance, lipid deposition and inflammation. However, the pathogenic mechanism of NAFLD is still poorly understood. Dual-specificity phosphatase 16 (DUSP16), a c-Jun N-terminal kinase-specific phosphatase, has been reported to negatively modulate the mitogen-activated protein kinases (MAPKs) signaling, and it has never been investigated in NAFLD progression. In the study, we identified that DUSP16 could directly interact with TAK1 in human hepatocytes. DUSP16 knockdown in the isolated primary hepatocytes stimulated by palmitate (PA) showed accelerated lipid deposition and inflammatory response, along with the exacerbated activation of c-Jun NH2-terminal kinase (JNK), Transforming growth factor beta (TGF-beta)-activated kinase (TAK1) and nuclear factor-kappaB (NF-kappaB) signaling pathways; however, the opposite results were detected in PA-treated hepatocytes with DUSP16 over-expression. The in vivo experiments confirmed that DUSP16 knockout significantly aggravated the metabolic disorder and insulin resistance in high fat diet (HFD)-challenged mice. In addition, HFD-provoked hepatic lipid accumulation and inflammation were further promoted in mice with DUSP16 knockout through the same molecular mechanism as detected in vitro. Herein, these findings demonstrated that DUSP16 could directly interact with TAK1 and negatively regulate JNK signaling to alleviate metabolic stress-induced hepatic steatosis, and thus could be considered as a promising new molecular target for NAFLD treatment. |
