RNase MCPIP1 regulates hepatic peroxisome proliferator-activated receptor gamma via TXNIP/PGC-1 alpha pathway

作     者：Pydyn, Natalia Kadluczka, Justyna Kus, Edyta Pospiech, Ewelina Losko, Magdalena Fu, Mingui Jura, Jolanta Kotlinowski, Jerzy 

作者机构：Jagiellonian Univ Fac Biochem Biophys & Biotechnol Dept Gen Biochem Gronostajowa 7 PL-30387 Krakow Poland Jagiellonian Univ Jagiellonian Ctr Expt Therapeut Bobrzynskiego 14 PL-30348 Krakow Poland Jagiellonian Univ Malopolska Ctr Biotechnol Krakow Poland Univ Missouri Sch Med Trauma Res Ctr Dept Biomed Sci & Shock Kansas City MO 64108 USA 

出 版 物：《BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS》 (生物化学与生物物理学报 - 类脂的分子和细胞生物学)

年 卷 期：2019年第000卷第10期

页      面：1458-1471页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：National Science Centre, Poland [2015/19/D/NZ5/00254] Polish Ministry of Science and Higher Education [BMN 2/2017, POIG.02.01.00-12-064/08, 02.02.00-00-014/08] Statutory Funds of the Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology (FBBB), Jagiellonian University European Union Ministry of Science and Higher Education 

主　　题：MCPIP1 Peroxisome proliferator-activated receptor gamma TXNIP Obesity Fatty liver 

摘      要：Monocyte chemoattractant protein-l-induced protein-1 (MCPIP1) acts as an endonuclease that degrades selected mRNAs, viral RNAs and pre-miRNAs. MCPIP1 inhibits adipogenesis by degradation of C/EBP beta 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 2-20 weeks and next primary hepatocytes and adipose tissue were isolated. For in vitro experiments we used murine primary hepatocytes, control HepG2 cells and HepG2 with over-expressed or silenced MCPIP1. We found that Mcpip1 levels were lower in primary hepatocytes isolated from HFD-fed mice than in control cells starting at 4 weeks 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 (PPAR gamma). This phenotype was reverted upon silencing of MCPIP1 in HepG2 cells and in primary hepatocytes lacking MCPIP1 protein. MCPIP1 activated the PPAR gamma transcription factor via the thioredoxin-interacting protein (TXNIP)/peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC-1 alpha) pathway. MCPIP1 contributes to lipid metabolism in hepatocytes by regulating the TXNIP/PGC-1 alpha/PPAR gamma pathway.