Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells
Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells
复制标题
AMP 激活蛋白激酶抑制剂化合物 C 对 3T3-L1 细胞成脂分化的影响
DOI：
10.1248/bpb.31.1716
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发表时间：
2008-09-01
影响因子：
2
通讯作者：
Wu, Donghai
中科院分区：
文献类型：
--
作者：
Gao, Ye;Zhou, Yi;Wu, Donghai
AMP激活的蛋白激酶（AMPK）在脂肪细胞分化中的作用还不完全清楚。在此，我们报道了AMPK抑制剂化合物C以剂量依赖性方式显著抑制3 T3-L1细胞的成脂分化，并且这种抑制作用主要在分化的初始阶段有效。化合物C可能通过抑制CCAAT/增强子结合蛋白（C/EBP）β和δ的表达来防止前脂肪细胞的有丝分裂克隆扩增（NICE），随后阻断C/EBP α和过氧化物酶体增殖物激活受体（PPAR）γ的表达以及产生脂肪细胞表型的基因的转录激活。AMPK活性在成脂分化的早期阶段也被化合物C处理抑制，这表明化合物C抑制AMPK的活化可能抑制前脂肪细胞的MCE过程。我们的研究结果表明，化合物C可能作为一个有用的分子，在基础和临床研究的脂肪形成和作为一个潜在的先导化合物，治疗肥胖。
The role of AMP-activated protein kinase (AMPK) in adipocyte differentiation is not completely understood. Here we reported that an AMPK inhibitor, compound C, significantly inhibited adipogenic differentiation of 3T3-L1 cells in a dose dependent manner, and this inhibitory effect was primarily effective in the initial stage of differentiation. Compound C prevented the mitotic clonal expansion (NICE) of preadipocytes, probably by hibiting expression of CCAAT/enhancer-binding protein (C/EBP)beta and delta, and subsequently blocked the expression of C/EBP alpha and peroxisome proliferator-activated receptor (PPAR)gamma and transcriptional activation of genes that produce the adipocyte phenotype. AMPK activity was also suppressed by compound C treatment during the early phase of adipogenic differentiation, which indicated that suppressed activation of AMPK by compound C may inhibit the MCE process of preadipocytes. Our results suggest that compound C might serve as a useful molecule in both basic and clinical research on adipogenesis and as a potential lead compound for the treatment of, obesity.