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榭皮素通过抑制有丝分裂克隆扩张来防止 3T3-L1 细胞脂肪细胞分化。

Inhibition of mitotic clonal expansion mediates fisetin-exerted prevention of adipocyte differentiation in 3T3-L1 cells.

机构信息

College of Pharmacy, Woosuk University, Jeollabuk-do, Wanju-gun, Korea.

出版信息

Arch Pharm Res. 2013 Nov;36(11):1377-84. doi: 10.1007/s12272-013-0226-z. Epub 2013 Aug 6.

DOI:10.1007/s12272-013-0226-z
PMID:23918651
Abstract

Adipocytes are the key player in adipose tissue inflammation and subsequent systemic insulin resistance and its development involves complex process of proliferation and differentiation of preadipocytes. Fistein, a polyphenol flavonoid, is known to exert anti-inflammatory, anti-carcinogenic and anti-diabetic effects. In this study, we aimed to investigate the effect of fisetin on adipocyte proliferation and differentiation in 3T3-L1 preadipocyte cell line and its mechanism of action. We found that fisetin inhibits adipocyte differentiation in a concentration dependent manner, which were evidenced by Oil Red O staining and the protein expression of mature adipocyte marker genes fatty acid synthase and peroxisome proliferator-activated receptor γ. Moreover, the proliferation of preadipocytes was also markedly suppressed by treatment of fisetin for 24 and 48 h in the differentiation medium. We also found that fisetin inhibition of adipocyte differentiation was largely due to the effect on mitotic clonal expansion. Fisetin suppression of preadipocyte proliferation at early stage of differentiation was accompanied by the changes of expression of a series of cell cycle regulatory proteins. Altogether, our results suggest that the inhibition of adipocyte differentiation by fisetin may be at least in part mediated by cell cycle arrest during adipogenesis.

摘要

脂肪细胞是脂肪组织炎症和随后的全身胰岛素抵抗的关键参与者,其发展涉及前脂肪细胞的增殖和分化的复杂过程。漆黄素是一种多酚类黄酮,已知具有抗炎、抗癌和抗糖尿病的作用。在本研究中,我们旨在研究漆黄素对 3T3-L1 前脂肪细胞系中脂肪细胞增殖和分化的影响及其作用机制。我们发现,漆黄素以浓度依赖的方式抑制脂肪细胞分化,这可以通过油红 O 染色和成熟脂肪细胞标记基因脂肪酸合酶和过氧化物酶体增殖物激活受体 γ 的蛋白表达来证明。此外,用漆黄素处理分化培养基 24 和 48 小时也明显抑制前脂肪细胞的增殖。我们还发现,漆黄素对脂肪细胞分化的抑制主要是由于对有丝分裂克隆扩张的影响。漆黄素在分化早期抑制前脂肪细胞增殖伴随着一系列细胞周期调节蛋白表达的变化。总之,我们的结果表明,漆黄素抑制脂肪细胞分化至少部分是通过脂肪生成过程中的细胞周期阻滞来介导的。

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