Masella Roberta, Varì Rosaria, D'Archivio Massimo, Santangelo Carmela, Scazzocchio Beatrice, Maggiorella Maria Teresa, Sernicola Leonardo, Titti Fausto, Sanchez Massimo, Di Mario Umberto, Leto Gaetano, Giovannini Claudio
National Centre for Food Quality and Risk Assessment, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
FEBS Lett. 2006 May 1;580(10):2421-9. doi: 10.1016/j.febslet.2006.03.068. Epub 2006 Mar 30.
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.
首次在3T3-L1前脂肪细胞中评估了氧化型低密度脂蛋白(oxLDL)对细胞增殖、凋亡和激素诱导分化的影响。与对照细胞不同,经oxLDL处理的前脂肪细胞显示出高增殖率、低凋亡水平,且分化过程受损,后期前脂肪细胞因子-1(Pref-1)mRNA表达增加。通过沉默Pref-1 mRNA或用增加的地塞米松浓度抑制其表达,分化照常发生,这证明了Pref-1过表达的关键作用。结果表明oxLDL对脂肪生成抑制剂Pref-1有特异性作用,在用oxLDL处理的成熟脂肪细胞中其再次出现也表明了这一点。oxLDL对分化的抑制作用需要CD36摄取oxLDL,且与脂蛋白脂质有关。这些结果表明oxLDL是脂肪组织量的调节剂,也是肥胖及其临床并发症之间可能的联系。