Characterization of the long pentraxin PTX3 as a TNFalpha-induced secreted protein of adipose cells.
Exposure of preadipocytes to long-chain fatty acids induces the expression of several markers of adipocyte differentiation. In an attempt to identify novel genes and proteins that are regulated by fatty acids in preadipocytes, we performed a substractive hybridization screening and identified PTX3, a protein of the pentraxin family. PTX3 mRNA expression is transient during adipocyte differentiation of clonal cell lines and is absent in fully differentiated cells. Stable overexpression of PTX3 in preadipocytes has no effect on adipocyte differentiation. In line with this, PTX3 mRNA is expressed in the stromal-vascular fraction of adipose tissue, but not in the adipocyte fraction; however, in 3T3-F442A adipocytes, the PTX3 gene can be reinduced by tumor necrosis factor alpha (TNFalpha) in a dose-dependent manner. This effect is accompanied by PTX3 protein secretion from both 3T3-F442A adipocytes and explants of mouse adipose tissue. PTX3 mRNA levels are found to be higher in adipose tissue of genetically obese mice versus control mice, consistent with their increased TNFalpha levels. In conclusion, PTX3 appears as a TNFalpha-induced protein that provides a new link between chronic low-level inflammatory state and obesity.
Abderrahim-Ferkoune
Anissa
A
Institute of Signaling, Developmental Biology and Cancer Research, Centre de Biochimie, UMR 6543 CNRS, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
Bezy
Olivier
O
Chiellini
Chiara
C
Maffei
Margherita
M
Grimaldi
Paul
P
Bonino
Frederic
F
Moustaid-Moussa
Naima
N
Pasqualini
Fabio
F
Mantovani
Alberto
A
Ailhaud
Gerard
G
Amri
Ez-Zoubir
EZ
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003920:Diabetes Mellitus / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D009765:Obesity; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000099153:Pentraxins
D002097:C-Reactive Protein; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins