| First Author | Pydyn N | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1864 |
| Issue | 10 | Pages | 1458-1471 |
| PubMed ID | 31185306 | Mgi Jnum | J:278358 |
| Mgi Id | MGI:6343100 | Doi | 10.1016/j.bbalip.2019.06.006 |
| Citation | Pydyn N, et al. (2019) RNase MCPIP1 regulates hepatic peroxisome proliferator-activated receptor gamma via TXNIP/PGC-1alpha pathway. Biochim Biophys Acta Mol Cell Biol Lipids 1864(10):1458-1471 |
| abstractText | Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) acts as an endonuclease that degrades selected mRNAs, viral RNAs and pre-miRNAs. MCPIP1 inhibits adipogenesis by degradation of C/EBPbeta mRNA and adipogenesis-related miRNA, however its role in the regulation of hepatic lipid homeostasis is unknown. In this study, we investigated the role of MCPIP1 in the regulation of lipid metabolism in hepatocytes. C57BL/6 mice were fed a high-fat diet (HFD) for 2-20weeks and next primary hepatocytes and adipose tissue were isolated. For in vitro experiments we used murine primary hepatocytes, control HepG2 cells and HepG2 with overexpressed or silenced MCPIP1. We found that Mcpip1 levels were lower in primary hepatocytes isolated from HFD-fed mice than in control cells starting at 4weeks of a HFD. Level of Mcpip1 was also depleted in visceral fat isolated from obese and glucose-intolerant mice characterized by fatty liver disease. We showed that MCPIP1 overexpression in HepG2 cells treated with oleate induces the level and activity of peroxisome proliferator-activated receptor gamma (PPARgamma). This phenotype was reverted upon silencing of MCPIP1 in HepG2 cells and in primary hepatocytes lacking Mcpip1 protein. MCPIP1 activated the PPARgamma transcription factor via the thioredoxin-interacting protein (TXNIP)/peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC-1alpha) pathway. MCPIP1 contributes to lipid metabolism in hepatocytes by regulating the TXNIP/PGC-1alpha/PPARgamma pathway. |
