TNFalpha up-regulates apelin expression in human and mouse adipose tissue.
We have recently identified apelin as a novel adipokine up-regulated by insulin and obesity. Since obesity and insulin resistance are associated with chronically elevated levels of both insulin and TNFalpha, the present study was performed to investigate a putative regulation of apelin expression in adipocytes by TNFalpha. Herein, we report a tight correlation between apelin and TNFalpha expression in adipose tissue of lean and obese humans. Apelin regulation by TNFalpha was further studied in cultured explants of human adipose tissue. The endogenous expression of TNFalpha in adipocytes isolated from the explants was accompanied by a 6-9 h subsequent increase of apelin expression in adipocytes. This increase was reversed by inhibiting TNFalpha expression with 100 microM isobutylmethylxanthine. In different mouse models of obesity, expression of both TNFalpha and apelin was also significantly increased in adipocytes of obese mice. Furthermore, short-term exposure to an i.p. injection of TNFalpha in C57Bl6/J mice induced an increase of apelin expression in adipose tissue as well as apelin plasma levels. Finally, a direct positive effect of TNFalpha has been shown in differentiated 3T3F442A adipocytes on apelin expression and secretion. The signaling pathways of TNFalpha for the induction of apelin were dependent of PI3-kinase, c-Jun NH2-terminal kinase (JNK), and MAPK but not PKC activation. All together, these findings suggest that apelin might be a candidate to better understand potential links between obesity and associated disorders such as inflammation and insulin resistance.
Daviaud
Danièle
D
INSERM, U586, Unité de recherches sur les obésités, Université Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse, France.
Boucher
Jérémie
J
Gesta
Stéphane
S
Dray
Cédric
C
Guigne
Charlotte
C
Quilliot
Didier
D
Ayav
Ahmet
A
Ziegler
Olivier
O
Carpene
Christian
C
Saulnier-Blache
Jean-Sébastien
JS
Valet
Philippe
P
Castan-Laurell
Isabelle
I
D016475:3T3 Cells; D000005:Abdomen; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D054392:Adipokines; D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D000818:Animals; D000073861:Apelin; D002352:Carrier Proteins; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C115436:APLN protein, human; D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha