Abstract
Regulation of the expression of GPCR fatty acid receptor genes has been examined in human adipocytes differentiated in culture. TNFα and IL-1β induced a marked reduction in GPR120 expression, mRNA level falling 17-fold at 24 h in adipocytes incubated with TNFα. In contrast, GPR84 mRNA was dramatically increased by these cytokines (>500-fold for IL-1β at 4 h); GPR41 expression was also stimulated. Rosiglitazone did not affect GPR84 expression, but GPR120 and GPR41 expression increased. Dexamethasone, insulin, linoleic and docosahexaenoic acids (DHA), and TUG891 (GPR120 agonist) had little effect on GPR120 and GPR84 expression. TUG891 did not attenuate the pro-inflammatory actions of TNFα and IL-1β. DHA slightly countered the actions of IL-1β on CCL2, IL6 and ADIPOQ expression, though not on secretion of these adipokines. GPR120 and GP84 gene expression in human adipocytes is highly sensitive to pro-inflammatory mediators; the inflammation-induced inhibition of GPR120 expression may compromise the anti-inflammatory action of GPR120 agonists.
Keywords:
Adipose tissue; docosahexaenoic acid; fatty acid sensors; inflammation.
MeSH terms
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Adult
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Anti-Inflammatory Agents / pharmacology
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Biphenyl Compounds / pharmacology
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Cells, Cultured
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Cytokines / genetics
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Cytokines / metabolism*
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Dexamethasone / pharmacology
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Docosahexaenoic Acids / metabolism
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Fatty Acids, Omega-3 / metabolism*
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Female
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Gene Expression Regulation* / drug effects
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Humans
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Hypoglycemic Agents / pharmacology
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Linoleic Acid / metabolism
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Middle Aged
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Phenylpropionates / pharmacology
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Receptors, Cell Surface / agonists*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled / agonists*
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Recombinant Proteins / metabolism
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Rosiglitazone
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Subcutaneous Fat / cytology
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Subcutaneous Fat / drug effects
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Subcutaneous Fat / immunology
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Subcutaneous Fat / metabolism*
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Thiazolidinediones / pharmacology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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3-(4-((4-fluoro-4'-methyl-(1,1'-biphenyl)-2-yl)methoxy)phenyl)propanoic acid
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Anti-Inflammatory Agents
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Biphenyl Compounds
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Cytokines
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FFAR3 protein, human
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FFAR4 protein, human
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Fatty Acids, Omega-3
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GPR84 protein, human
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Hypoglycemic Agents
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IL1B protein, human
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Interleukin-1beta
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Phenylpropionates
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Recombinant Proteins
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TNF protein, human
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Thiazolidinediones
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Tumor Necrosis Factor-alpha
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Rosiglitazone
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Docosahexaenoic Acids
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Dexamethasone
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Linoleic Acid