GPR103b functions in the peripheral regulation of adipogenesis.
The activation of G protein-coupled receptor 103 (GPR103) by its endogenous peptidic ligands, QRFPs, is involved in the central regulation of feeding by increasing food intake, body weight, and fat mass after intracerebroventricular injection in mice. However, the role of GPR103 in regulating peripheral metabolic pathways has not yet been explored. The present study aimed to investigate the role of GPR103 in adipogenesis and lipid metabolism using 3T3-L1 adipocyte cells. Our results show that differentiated 3T3-L1 cells expressed the GPR103b subtype mRNA and protein, as well as QRFP mRNA. QRFP-43 and -26 induced an increase in triglyceride accumulation of 50 and 41%, respectively, and elicited a dose-dependent increase in fatty acid uptake, by up to approximately 60% at the highest concentration, in 3T3-L1-differentiated cells. QRFP-43 and -26 inhibited isoproterenol (ISO)-induced lipolysis in a dose-dependent manner, with IC(50)s of 2.3 +/- 1.2 and 1.1 +/- 1.0 nm, respectively. The expression of genes involved in lipid uptake (FATP1, CD36, LPL, ACSL1, PPAR-gamma, and C/EBP-alpha), was increased by 2- to 3-fold after treatment with QRFP. The effects of QRFP on ISO-induced lipolysis and fatty acid uptake were abolished when GPR103b was silenced. In a mouse model of diet-induced obesity, the expression of GPR103b in epididymal fat pads was elevated by 16-fold whereas that of QRFP was reduced by 46% compared to lean mice. Furthermore, QRFP was bioactive in omental adipocytes from obese individuals, inhibiting ISO-induced lipolysis in these cells. Our results suggest that GPR103b and QRFP work in an autocrine/paracrine manner to regulate adipogenesis.
Faculty of Pharmacy, Université de Montréal Case Postale 6128, Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7. huy.ong@umontreal.ca.
Mukandila
M
Mulumba
Christian
C
Jossart
Riccarda
R
Granata
Davide
D
Gallo
Emanuel
E
Escher
Ezio
E
Ghigo
Marc J
MJ
Servant
Sylvie
S
Marleau
Huy
H
Ong
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C511787:QRFP peptide; C539769:QRFP-26 peptide; C476583:Qrfpr protein, mouse; D043562:Receptors, G-Protein-Coupled; D007545:Isoproterenol