Oxidised LDL modulate adipogenesis in 3T3-L1 preadipocytes by affecting the balance between cell proliferation and differentiation.
The effects of oxidised LDL (oxLDL) on cell proliferation, apoptosis and hormone-induced differentiation have been evaluated for the first time in 3T3-L1 preadipocytes. Unlike control cells, oxLDL-treated preadipocytes showed a high proliferation rate, a low apoptosis level, and an impaired differentiation process with an increased preadipocyte factor-1 (Pref-1) mRNA expression at late times. By silencing Pref-1 mRNA or inhibiting its expression with an increased dexamethasone concentration, differentiation occurred as usual, which demonstrates the key role of Pref-1 overexpression. The results suggest a specific action of oxLDL on the adipogenesis inhibitor Pref-1, as indicated also by its reappearance in mature adipocytes treated with oxLDL. The inhibitory effects of oxLDL on differentiation required oxLDL uptake by CD36, and were associated with lipoprotein lipids. These results point to oxLDL as a modulator of adipose tissue mass and as possible link between obesity and its clinical complications.
Masella
Roberta
R
National Centre for Food Quality and Risk Assessment, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. masellar@iss.it
Varì
Rosaria
R
D'Archivio
Massimo
M
Santangelo
Carmela
C
Scazzocchio
Beatrice
B
Maggiorella
Maria Teresa
MT
Sernicola
Leonardo
L
Titti
Fausto
F
Sanchez
Massimo
M
Di Mario
Umberto
U
Leto
Gaetano
G
Giovannini
Claudio
C
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C099252:oxidized low density lipoprotein