Kim Su-Nam, Choi Hye-Young, Kim Yong Kee
KIST Gangneung Institute, Gangneung, 210-340, Korea.
Arch Pharm Res. 2009 Apr;32(4):535-41. doi: 10.1007/s12272-009-1409-5. Epub 2009 Apr 29.
In this study, we investigated the effects of various histone deacetylase (HDAC) inhibitors on adipocyte differentiation. Treatment of 3T3-L1 cells with HDAC inhibitors such as apicidin, trichostatin A, or suberoylanilide hydroxamic acid, under conditions that normally promote differentiation led to a dramatic attenuation of adipocyte differentiation. In contrast, sodium butyrate (NaB) treatment increased adipocyte differentiation. Accordingly, the expression of adipogenic marker genes such as FAS, aP2, PPARgamma, resistin, C/EBPalpha, ADD1/SREBP1c, and adiponectin were inhibited by apicidin treatment but not NaB, indicating that the adipocyte differentiation process could be differentially regulated depending on the type of HDAC inhibitor utilized. In addition, this differential effect seemed not to be due to disruption of the insulin- signaling pathway. Interestingly, our data showed that apicidin treatment could induce dedifferentiation of fully differentiated adipocytes, as evident by the fact that apicidin treatment led to a decrease of Oil Red O-stained adipocytes with a concomitant reduction in the expression levels of adipogenic marker genes. Collectively, our results suggest that adipocyte differentiation and dedifferentiation may be regulated by HDAC inhibitors.
在本研究中，我们调查了各种组蛋白去乙酰化酶（HDAC）抑制剂对脂肪细胞分化的影响。在通常促进分化的条件下，用HDAC抑制剂如阿皮西丁、曲古抑菌素A或辛二酰苯胺异羟肟酸处理3T3-L1细胞，导致脂肪细胞分化显著减弱。相比之下，丁酸钠（NaB）处理则增加了脂肪细胞分化。因此，阿皮西丁处理可抑制脂肪酸合酶（FAS）、脂肪细胞脂肪酸结合蛋白2（aP2）、过氧化物酶体增殖物激活受体γ（PPARγ）、抵抗素、CCAAT/增强子结合蛋白α（C/EBPα）、脂肪分化相关蛋白1/固醇调节元件结合蛋白1c（ADD1/SREBP1c）和脂联素等脂肪生成标记基因的表达，但NaB处理则不会，这表明脂肪细胞分化过程可能因所使用的HDAC抑制剂类型不同而受到差异调节。此外，这种差异效应似乎并非由于胰岛素信号通路的破坏所致。有趣的是，我们的数据表明，阿皮西丁处理可诱导完全分化的脂肪细胞去分化，这一点从阿皮西丁处理导致油红O染色的脂肪细胞减少以及脂肪生成标记基因表达水平随之降低可以明显看出。总体而言，我们的结果表明脂肪细胞分化和去分化可能受HDAC抑制剂调控。
