Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner.
Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner.
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DOI：
10.1038/s41598-017-06761-4
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发表时间：
2017-07-26
影响因子：
4.6
通讯作者：
Nangaku M
中科院分区：
文献类型：
--
作者：
Yamaguchi J;Tanaka T;Saito H;Nomura S;Aburatani H;Waki H;Kadowaki T;Nangaku M
肥胖是许多疾病的危险因素，包括糖尿病、癌症、心血管疾病和慢性肾脏疾病。肥胖的特征是白色脂肪组织（WAT）的扩张。脂肪细胞的肥大和增生引起组织缺氧，引起炎症和纤维化。它的触发因子，前脂肪细胞分化为成熟脂肪细胞，受到转录因子、信号分子和辅助因子的精细调节。我们发现棘霉素是一种有效的HIF-1抑制剂，通过影响有丝分裂克隆扩增的早期阶段，完全抑制3T3-L1 WAT前脂肪细胞的脂肪形成。发挥效果所需的剂量低得惊人，时间也短得惊人。有趣的是，它的抑制作用与HIF-1途径无关。对药物处理和未处理的前脂肪细胞进行时程DNA芯片分析，提取了一个主要的转录因子，CCAAT/增强蛋白β，作为青霉霉素的关键靶点。紫霉素还能抑制高脂饮食小鼠的脂肪生成和体重增加。这些发现强调了紫霉素在抑制脂肪细胞分化中的新作用，并为肥胖和糖尿病的治疗提供了新的策略。
Obesity is a risk factor for many diseases including diabetes, cancer, cardiovascular disease, and chronic kidney disease. Obesity is characterized by the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of adipocytes cause tissue hypoxia followed by inflammation and fibrosis. Its trigger, preadipocyte differentiation into mature adipocytes, is finely regulated by transcription factors, signal molecules, and cofactors. We found that echinomycin, a potent HIF-1 inhibitor, completely inhibited adipogenesis in 3T3-L1 WAT preadipocytes by affecting the early phase of mitotic clonal expansion. The dose required to exert the effect was surprisingly low and the time was short. Interestingly, its inhibitory effect was independent of HIF-1 pathways. Time-course DNA microarray analysis of drug-treated and untreated preadipocytes extracted a major transcription factor, CCAAT/enhancer-protein β, as a key target of echinomycin. Echinomycin also inhibited adipogenesis and body weight gain in high fat diet mice. These findings highlight a novel role of echinomycin in suppressing adipocyte differentiation and offer a new therapeutic strategy against obesity and diabetes.
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影响因子：
64.5
作者：
Lee YS;Kim JW;Osborne O;Oh DY;Sasik R;Schenk S;Chen A;Chung H;Murphy A;Watkins SM;Quehenberger O;Johnson RS;Olefsky JM
通讯作者：
Olefsky JM
影响因子：
29
作者：
Lee KY;Gesta S;Boucher J;Wang XL;Kahn CR
通讯作者：
Kahn CR
DOI：
10.1073/pnas.91.19.8757
发表时间：
1994-09-13
影响因子：
11.1
作者：
LIN, FT;LANE, MD
通讯作者：
LANE, MD
DOI：
10.1093/bioinformatics/btu743
发表时间：
2015-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Naito Y;Hino K;Bono H;Ui-Tei K
通讯作者：
Ui-Tei K
影响因子：
3.5
作者：
Burton, GR;Nagarajan, R;McGehee, RE
通讯作者：
McGehee, RE