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首页> 外文期刊>Molecular and Cellular Biology >Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma.
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Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma.

机译：在诱导PPARγ后，类维生素A抑制分化，从而揭示了脂肪形成的不同阶段。

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Retinoic acid (RA) inhibits adipocyte differentiation of 3T3-L1 preadipocytes but is effective only early in adipogenesis. RA prevented induction of the adipogenic factors PPARgamma and C/EBPalpha. Using receptor-specific ligands, we determined that the effects of RA were mediated by liganded RA receptors (RARs) rather than retinoid X receptors. Preadipocytes expressed primarily RARalpha and RARgamma; during adipocyte differentiation, RARalpha gene expression was nearly constant, whereas RARgamma1 mRNA and protein levels dramatically decreased. Ectopic expression of RARgamma1 extended the period of effectiveness of RA by 24 to 48h; RARalpha expression had a similar effect, suggesting functional redundancy of RAR subtypes. Remarkably, RA inhibited differentiation when added after PPARgamma1 and PPARgamma2 proteins had already been expressed and resulted in the loss of PPARgamma proteins from cells. By 72 to 96 h after the induction of differentiation, RA failed to prevent differentiation of even ectopic-RAR-expressing cells. Thus, the unresponsiveness of 3T3-L1 preadipocytes to RA after the induction of differentiation is initially due to the reduction in cellular RAR concentration rather than to the induction of PPARgamma. At later times cells continue along the differentiation pathway in a manner which is RA and RAR independent.
机译：维甲酸（RA）抑制3T3-L1前脂肪细胞的脂肪细胞分化，但仅在脂肪形成的早期有效。 RA阻止了脂肪形成因子PPARgamma和C / EBPalpha的诱导。使用受体特异性配体，我们确定RA的作用是由配体RA受体（RAR）而非类维生素A X受体介导的。前脂肪细胞主要表达RARalpha和RARgamma。在脂肪细胞分化过程中，RARalpha基因表达几乎恒定，而RARgamma1 mRNA和蛋白质水平急剧下降。 RARgamma1的异位表达将RA的有效期延长了24至48h。 RARalpha表达具有类似的作用，表明RAR亚型的功能冗余。值得注意的是，当PPARgamma1和PPARgamma2蛋白已经表达后添加时，RA抑制分化，并导致PPARgamma蛋白从细胞中丢失。诱导分化后72至96小时，RA未能阻止甚至表达异位RAR的细胞的分化。因此，分化诱导后3T3-L1前脂肪细胞对RA的无反应性起初是由于细胞RAR浓度的降低而不是由于PPARγ的诱导。在以后的时间，细胞以独立于RA和RAR的方式继续沿着分化途径前进。

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