The RFamide peptides QRFPs have been recently identified as endogenous ligands of the orphan G protein-coupled receptors GPR103a and b, expressed in hypothalamic regions involved in the regulation of orexigenic activity. ICV injection of QRFPs induced hyperphagia, leading to an increase in body weight and fat mass. However, whether the adipogenic effect results from the direct action of QRFP on adipose tissue has yet to be determined. Objectives: 1) to document the expression of GPR103 in primary mice adipocytes and 3T3-L1 preadipocytes upon their differentiation process; 2) to characterize the role of GPR103 in mediating the fatty acid uptake and the modulating effect of QRFPs on lypolysis; 3) To assess the role of GPR103 in mediating the effect of QRFPs in adipogenesis. Results: The GPR103b receptor subtype has been found expressed selectively in 3T3-L1 preadipocytes during differentiation, in a time-dependent manner. The increase of C12 Bodipy free acid (FA) uptake of 27 ± 3% induced by QRFP-43 is abolished following infection with specific shRNA for GPR103b. QRFP 43 features an antilipolytic effect on isoproterenol-induced lipolysis which vanishes following GPR103b knock down in differentiated 3T3-L1 cells. GPR103b appears to mediate the effect of QRFP-43 in promoting adipogenic genes (PPARγ-C/EBPα, FATP1, ACSL1) in differentiated 3T3 adipocytes expressing this receptor. Conclusion: GPR103b appears to modulate adipogenesis not only in the brain but also at the level of peripheral adipose tissues, suggesting GPR103b as a potential target in the treatment of obesity. Supported by an educational grant of Aeterna Zentaris Inc.
Role of GPR103b, a new G-protein coupled receptor, in the peripheral regulation of adipogenesis
GRANATA, Riccarda;GHIGO, Ezio;
2010-01-01
Abstract
The RFamide peptides QRFPs have been recently identified as endogenous ligands of the orphan G protein-coupled receptors GPR103a and b, expressed in hypothalamic regions involved in the regulation of orexigenic activity. ICV injection of QRFPs induced hyperphagia, leading to an increase in body weight and fat mass. However, whether the adipogenic effect results from the direct action of QRFP on adipose tissue has yet to be determined. Objectives: 1) to document the expression of GPR103 in primary mice adipocytes and 3T3-L1 preadipocytes upon their differentiation process; 2) to characterize the role of GPR103 in mediating the fatty acid uptake and the modulating effect of QRFPs on lypolysis; 3) To assess the role of GPR103 in mediating the effect of QRFPs in adipogenesis. Results: The GPR103b receptor subtype has been found expressed selectively in 3T3-L1 preadipocytes during differentiation, in a time-dependent manner. The increase of C12 Bodipy free acid (FA) uptake of 27 ± 3% induced by QRFP-43 is abolished following infection with specific shRNA for GPR103b. QRFP 43 features an antilipolytic effect on isoproterenol-induced lipolysis which vanishes following GPR103b knock down in differentiated 3T3-L1 cells. GPR103b appears to mediate the effect of QRFP-43 in promoting adipogenic genes (PPARγ-C/EBPα, FATP1, ACSL1) in differentiated 3T3 adipocytes expressing this receptor. Conclusion: GPR103b appears to modulate adipogenesis not only in the brain but also at the level of peripheral adipose tissues, suggesting GPR103b as a potential target in the treatment of obesity. Supported by an educational grant of Aeterna Zentaris Inc.
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