title: Apelin, a newly identified adipokine up-regulated by insulin and obesity.
abstract: The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 586, Institut Fédératif de Recherche 31, Centre Hospitalier Universitaire Rangueil, BP 84225 F-31432 Toulouse Cedex 4, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Boucher
authors.forename: Bernard
authors.initials: B
authors.lastname: Masri
authors.forename: Danièle
authors.initials: D
authors.lastname: Daviaud
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gesta
authors.forename: Charlotte
authors.initials: C
authors.lastname: Guigné
authors.forename: Anne
authors.initials: A
authors.lastname: Mazzucotelli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Castan-Laurell
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.forename: Bernard
authors.initials: B
authors.lastname: Knibiehler
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
authors.forename: Yves
authors.initials: Y
authors.lastname: Audigier
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Saulnier-Blache
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D054392:Adipokines; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000073861:Apelin; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C115436:APLN protein, human; D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D002352:Carrier Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins