The purinergic P2Y1 receptor supports leptin secretion in adipose tissue.
Extracellular nucleotides have been shown to trigger intracellular calcium release and influence leptin secretion in differentiated white and brown adipocytes through activation of various but not clearly identified P2 receptors. In the present study, we wished to assess whether or not the P2Y1 ADP receptor is functional in white adipocytes and whether it could affect the secretion of adipocyte-derived hormones. Stromal cells and mature adipocytes were isolated from epididymal adipose tissue from wild-type and P2Y1 knockout (KO) C57-black/six male mice. The expression of the P2Y1 receptor in adipocytes was confirmed by RT-PCR and intracellular calcium measurements with fura 2-AM. KO of P2Y1 receptors did not affect the cell size and lipid content of mature adipocytes or the differentiation of the stromal cell fraction, but the leptin production of mature adipocytes was decreased under basal and insulin-stimulated conditions. A selective P2Y1 antagonist, MRS2500, reduced leptin release in isolated adipocytes. The plasma and adipose tissue mRNA levels of leptin were also lower in P2Y1 KO mice as compared with wild-type animals. However, in mice fed a high-fat diet, the plasma leptin levels were greatly enhanced and the inhibitory effect of P2Y1 KO was not observed. These results show that the P2Y1 receptor supports leptin production in isolated white adipocytes through a transcriptional mechanism. This function of the receptor may regulate plasma leptin in lean mice but is overcome in obese animals.
Laplante
Marc-André
MA
Unité Mixte de Recherche S949 Institut National de la Santé et de la Recherche Médicale-Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg Cedex, France.
Monassier
Laurent
L
Freund
Monique
M
Bousquet
Pascal
P
Gachet
Christian
C
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000032:analysis; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D048429:Cell Size; D002478:Cells, Cultured; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology; D004822:Epididymis / Q000378:metabolism; D015870:Gene Expression; D020738:Leptin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
C495475:2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate; D052242:Adiponectin; D003838:Deoxyadenine Nucleotides; D020738:Leptin; D008055:Lipids; C546383:P2ry1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D002118:Calcium