Basic Research
Mechanism of GPR119 in regulating lipid metabolism and anti-atherosclerosis by hypoxia-inducible factor-1α/ vascular endothelial growth factor pathway
Chen Zhiping, Wang Yufeng, Zhong Jinghua, Xi Xuxiang, Wu Xiangsheng
Published 2019-12-25
Cite as Chin J Endocrinol Metab, 2019,35(12): 1055-1060. DOI: 10.3760/cma.j.issn.1000-6699.2019.12.011
Abstract
ObjectiveTo investigate the effect and mechanism of G protein coupled receptor 119 (GPR119) in regulating lipid metabolism.
Methods(1) Macrophage THP-1 was induced by oxidized low density lipoprotein (oxLDL) to the formation of lipid foam cells, protein expression of GPR119, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) were detected by Western blotting. (2) Constructing GPR119 over-expressed and low-expressed plasmids, the plasmids were transfected into THP-1 cells which induced by oxLDL. The lipid content in macrophages was observed by oil red O staining. Cholesterol efflux was detected by liquid scintillation counter. The mRNA and protein expressions of HIF-1α, VEGF were detected by reverse transcription PCR and Western blotting. (3) Constructing GPR119, HIF-1α, and VEGF over-expressed plasmids, then co-transfection of GPR119 and HIF-1α/VEGF plasmids. The lipid content in macrophages was observed by oil red O staining. Cholesterol efflux was detected by liquid scintillation counter.
ResultsCompared with the control group, the lipid droplets were densely distributed in macrophages, with a large number and volume. The protein expression of GPR119 was significantly decreased and HIF-1α, VEGF were significantly increased in macrophages induced by oxLDL (P<0.05). After over-expression of GPR119, the lipid droplets were sparsely distributed and the number was significantly reduced in macrophages, the lipid droplets were mostly located in the area around the cells. The cholesterol efflux was significantly increased (P<0.01). The mRNA and protein expressions of HIF-1α and VEGF were significantly decreased (P<0.01). On the contrary, in the GPR119 inhibition group, the lipid droplets were densely distributed in macrophages, with a large number and volume. The lipid droplets even covered the nuclei. The cholesterol efflux was significantly reduced (P<0.05). The mRNA and protein expression of HIF-1α, VEGF were significantly increased (P<0.05). After GPR119 were co-expressed with HIF-1α and VEGF, the number of lipid droplets was increased, lipid droplets were dense and bulky in oxLDL-induce macrophages. The cholesterol efflux was inhibited.
ConclusionGPR119 can regulate lipid metabolism and possibly by down-regulating the expression of HIF-1α and VEGF.
Key words:
GPR119; Lipid metabolism; Atherosclerosis; HIF-1α; VEGF
Contributor Information
Chen Zhiping
Department of Clinical Laboratory, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China
Wang Yufeng
Department of Nephrology, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China
Zhong Jinghua
Department of Oncology, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China
Xi Xuxiang
Department of Clinical Laboratory, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China
Wu Xiangsheng
Department of Clinical Laboratory, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China
