A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis.
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 and inflammation in THP-1 macrophages and atherosclerotic plaque progression in apoE(-/-) mice. We found that oxidized LDL (Ox-LDL) significantly induced long intervening noncoding RNA (lincRNA)-DYNLRB2-2 expression, resulting in the upregulation of GPR119 and ABCA1 expression through the glucagon-like peptide 1 receptor signaling pathway. GPR119 significantly decreased cellular cholesterol content and increased apoA-I-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. In vivo, apoE(-/-) mice were randomly divided into two groups and infected with lentivirus (LV)-Mock or LV-GPR119 for 8 weeks. GPR119-treated mice showed decreased liver lipid content and plasma TG, interleukin (IL)-1β, IL-6, and TNF-α levels, whereas plasma levels of apoA-I were significantly increased. Consistent with this, atherosclerotic lesion development was significantly inhibited by infection of apoE(-/-) mice with LV-GPR119. Our findings clearly indicate that, Ox-LDL significantly induced lincRNA-DYNLRB2-2 expression, which promoted ABCA1-mediated cholesterol efflux and inhibited inflammation through GPR119 in THP-1 macrophage-derived foam cells. Moreover, GPR119 decreased lipid and serum inflammatory cytokine levels, decreasing atherosclerosis in apoE(-/-) mice. These suggest that GPR119 may be a promising candidate as a therapeutic agent.
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yan-Wei
YW
Hu
Jun-Yao
JY
Yang
Xin
X
Ma
Zhi-Ping
ZP
Chen
Ya-Rong
YR
Hu
Jia-Yi
JY
Zhao
Shu-Fen
SF
Li
Yu-Rong
YR
Qiu
Jing-Bo
JB
Lu
Yan-Chao
YC
Wang
Ji-Juan
JJ
Gao
Yan-Hua
YH
Sha
Lei
L
Zheng
Qian
Q
Wang
D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006706:Homeostasis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016207:Cytokines; C000593833:GLP1R protein, human; C519854:GPR119 protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018836:Inflammation Mediators; D008055:Lipids; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D062085:RNA, Long Noncoding; D043562:Receptors, G-Protein-Coupled; D018027:Receptors, Glucagon; C099252:oxidized low density lipoprotein; D002784:Cholesterol
ATP binding cassette transporter A1; G protein-coupled receptor 119; atherosclerosis; glucagon-like peptide 1 receptor; long intervening noncoding ribonucleic acid-DYNLRB2-2