A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis

• DOI: 10.1194/jlr.m044669
• Publication Date: 2014-02-04T02:02:28Z
• Authors: Yan-Wei Hu; Jun-Yao Yang; Xin Ma; Zhi-Ping Chen; Ya-Rong Hu; Jia-Yi Zhao; Shu-Fen Li; Yu-Rong Qiu; Jing-Bo Lu; Yan-Chao Wang; Ji-Juan Gao; Yan-Hua Sha; Lei Zheng; Qian Wang
• Keywords: Liver X receptor; Apolipoprotein E

Accumulated evidence shows that G protein-coupled receptor 119 (GPR119) plays a key role in glucose and lipid metabolism. Here, we explored the effect of GPR119 on cholesterol metabolism inflammation THP-1 macrophages atherosclerotic plaque progression apoE(-/-) mice. We found oxidized LDL (Ox-LDL) significantly induced long intervening noncoding RNA (lincRNA)-DYNLRB2-2 expression, resulting upregulation ABCA1 expression through glucagon-like peptide 1 signaling pathway. decreased cellular content increased apoA-I-mediated efflux macrophage-derived foam cells. In vivo, mice were randomly divided into two groups infected with lentivirus (LV)-Mock or LV-GPR119 for 8 weeks. GPR119-treated showed liver plasma TG, interleukin (IL)-1β, IL-6, TNF-α levels, whereas levels apoA-I increased. Consistent this, lesion development was inhibited by infection LV-GPR119. Our findings clearly indicate that, Ox-LDL lincRNA-DYNLRB2-2 which promoted ABCA1-mediated Moreover, serum inflammatory cytokine decreasing atherosclerosis These suggest may be promising candidate as therapeutic agent.