Studies on adipose tissue development

明确脂肪细胞增殖和分化的正、负调控系统对改善人类健康具有重要意义。各种营养或药理学试剂已显示影响体内和体外脂肪转化。特别是维甲酸（RA）和1，25-二羟维生素D3（1，25-OH 2D 3）对脂肪细胞的分化有抑制作用，但脂溶性维生素对前脂肪细胞向脂肪细胞生长和分化的影响还没有系统的研究。在本研究中，我们决定系统地研究这些脂溶性维生素及其类似物对前脂肪细胞向脂肪细胞终末分化的细胞和分子方面的影响。RA和1，25-OH 2D 3的作用被认为是由特异性核受体蛋白[视黄酸受体（RAR）;命名为α、β和γ亚型，维生素D受体（VDR）]介导的，视黄酸受体是配体依赖性转录调节因子的类固醇和甲状腺/类维生素A受体超家族的成员。用北方印迹法检测了这些受体在大鼠脂肪组织和3 T3-L1脂肪细胞系中的表达，结果表明，这些核受体亚家族的成员以异二聚体或同二聚体的形式与类维生素A X受体（RXR）结合。RA和1，25-OH 2D 3在脂肪组织中的RAR、RXR和VDR之间的相互作用的性质可能被证明对于理解脂肪形成的过程是重要的。

It is important to the improvement of human health that the positive and negative regulatory systems for the proliferation and differentiation of adipocytes be well defined. Various nutritional or pharmacological agents have been shown to affect adipose conversion in vivo and in vitro. In particular, it was reported that retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-OH2D3) inhibited the differentiation of adipocytes in cultured cells.However, the effects of fat soluble vitamins on growth and differentiation, preadipocytes to adipocytes, have not been investigated systematically. In the present study, we have decided to systematically examine the effects of these fat soluble vitamins and their analogs on terminal differentiation from preadipocytes to adipocytes on the cellular and molecular aspects. The effects of RA and 1,25-OH2D3 are believed to be mediated by a specific nuclear receptor protein [retinoic acid receptor (RAR) ; designated as subtypes alpha, beta and gamma, vitamin D receptor (VDR) ] which are members of the steroid and thyroid/retinoid receptor superfamily of ligand dependent transcriptional regulators. The expression of these receptors was examined by Northern blot analysis in rat adipose tissue and 3T3-L1 adipose cell line.Members of the retinoid/thyroid/vitamin D subfamily of nuclear receptors have been shown to bind their response elements as heterodimers with retinoid X receptor (RXR) or as homodimers. The nature of the cross-talk of RA and 1,25-OH2D3 actions between the RARs, RXRs and VDR in adipose tissue will likely prove to be important for understanding the process of adipogenesis.