Back to Search
Start Over
GPR120 in adipocytes has differential roles in the production of pro-inflammatory adipocytokines
- Source :
- Biochemical and biophysical research communications. 486(1)
- Publication Year :
- 2017
-
Abstract
- How nutritional excess leads to inflammatory responses in metabolic syndrome is not well characterized. Here, we evaluated the effects of ω-3 polyunsaturated fatty acid specific G-protein coupled receptor 120 (GPR120) activation on inflammatory pathways in adipocytes, and the influence of this process on macrophage migration. Using 3T3-L1 adipocytes, we found that agonizing GPR120 using its synthetic ligand, GSK137647, attenuated both basal and lipopolysaccharide-induced production of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2). Moreover, the intervention reduced the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and nuclear translocation of nuclear factor kappa-B p65 subunit (p65). Furthermore, the silencing of GPR120 itself reduced IL-6 and CCL2 mRNA expression. Inhibition of protein kinase C (PKC) augmented the down-regulatory effect of GSK137647 on IL-6 and CCL2 mRNA. Using a luciferase assay to measure promoter activity of the IL-6 gene in mouse embryonic fibroblasts, we demonstrated that exogenous transfection of GPR120 alone reduced the promoter activity, which was augmented by GSK137647. Inhibition of PKC further reduced the promoter activity. Nevertheless, RAW 264.7 macrophages grown in conditioned medium collected from GSK137647-treated adipocytes attenuated the expressions of matrix metalloproteinases-9 and -3, and tissue inhibitor of metalloproteinase-1. Conditioned medium also inhibited the lipopolysaccharide-induced migration of these macrophages. Taken together, these findings provide critical evidence that although GPR120 is associated with a PKC-mediated pro-inflammatory pathway, the direct inhibitory effects of GPR120 on the nuclear factor kappa B pathway are anti-inflammatory. Moreover, GPR120 activity can attenuate the adipocyte-mediated enhanced production of extracellular matrix-modulating factors in macrophages and can reduce their migration by a paracrine mechanism.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Chemokine
Blotting, Western
Biophysics
CCL2
Biochemistry
Cell Line
Receptors, G-Protein-Coupled
03 medical and health sciences
Mice
0302 clinical medicine
Adipokines
NF-KappaB Inhibitor alpha
Cell Movement
3T3-L1 Cells
Adipocytes
Gene silencing
Animals
Phosphorylation
Receptor
Molecular Biology
Protein kinase C
Cells, Cultured
Chemokine CCL2
Protein Kinase C
Tissue Inhibitor of Metalloproteinase-1
biology
Interleukin-6
Reverse Transcriptase Polymerase Chain Reaction
Macrophages
Transcription Factor RelA
GPR120
Cell Biology
Cell biology
IκBα
030104 developmental biology
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
biology.protein
Matrix Metalloproteinase 3
RNA Interference
Inflammation Mediators
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 486
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....12933c30c47607d82db1d81a5dd075d0