Apelin, a newly identified adipokine up-regulated by insulin and obesity.
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.
Boucher
Jérémie
J
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.
Masri
Bernard
B
Daviaud
Danièle
D
Gesta
Stéphane
S
Guigné
Charlotte
C
Mazzucotelli
Anne
A
Castan-Laurell
Isabelle
I
Tack
Ivan
I
Knibiehler
Bernard
B
Carpéné
Christian
C
Audigier
Yves
Y
Saulnier-Blache
Jean-Sébastien
JS
Valet
Philippe
P
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
C115436:APLN protein, human; D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D002352:Carrier Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins