Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.
Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.
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AKT1的过表达增强了脂肪形成，并导致斑马鱼中的脂肪瘤形成。
DOI：
10.1371/journal.pone.0036474
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hsiao CD
中科院分区：
文献类型：
--
作者：
Chu CY;Chen CF;Rajendran RS;Shen CN;Chen TH;Yen CC;Chuang CK;Lin DS;Hsiao CD
肥胖是一种复杂的、多因素的疾病，受遗传、表观遗传和环境因素的相互作用影响。肥胖增加了患许多慢性疾病或代谢综合征的风险。研究人员已经建立了几种哺乳动物肥胖模型来研究其潜在机制。然而，为了方便地进行肥胖药物筛选，一种较低的脊椎动物模型仍然是难以捉摸的。本研究的具体目的是通过过表达Akt1基因的胰岛素信号中枢来建立斑马鱼肥胖模型。皮肤致癌转化筛选表明，一种稳定的Tg（krt4Hsa）转基因斑马鱼。myrAkt1)cy18在成年期表现出严重的肥胖表型。在Tg (krt4:保险公司。myrAkt1)cy18，外源性人组成活性Akt1 （myrAkt1）的表达可以激活内源性下游靶点mTOR、GSK-3α/β和70S6K。在胚胎到幼虫过渡期，myrAkt1在皮肤中的特异性过表达可以促进增生性和增生性生长。从受精后21小时（hpf）开始，myrAkt1转基因在几个间充质衍生组织中异位表达。这可能是整合位置效应的结果。Tg (krt4:保险公司。myrAkt1)cy18在成虫期引起体重快速增加、脂肪细胞增生、脂肪组织异常堆积、血糖不耐受。实时RT-PCR分析显示，在Tg(krt4:Hsa.myrAkt1)cy18中，大部分调节脂肪生成、脂肪细胞因子和炎症的关键基因都高度上调。相反，在Tg（krt4:Hsa）中，肌生成和骨骼生成相关基因转录物显著下调。myrAkt1)cy18，表明脂肪细胞的过度分化是以牺牲其他间充质衍生组织为代价的。总的来说，本研究的发现提供了直接证据，证明Akt1信号在体内平衡正常脂肪组织水平中起重要作用。本研究中研究的肥胖斑马鱼可能成为筛选治疗人类肥胖的新药的有力模型。
Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene. Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)cy18 displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues. Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.
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影响因子：
3.8
作者：
Gleeson, M.;Connaughton, V.;Arneson, L. S.
通讯作者：
Arneson, L. S.
影响因子：
4
作者：
Dooley, K;Zon, LI
通讯作者：
Zon, LI
DOI：
10.1006/bbrc.1998.8637
发表时间：
1998-05-19
影响因子：
3.1
作者：
Christoffersen, CT;Tornqvist, H;Joshi, RL
通讯作者：
Joshi, RL
影响因子：
64.5
作者：
Chen, H;Charlat, O;Morgenstern, JP
通讯作者：
Morgenstern, JP
影响因子：
4.6
作者：
Hsieh, Shu-Chen;Chen, Nien-Tsu;Lo, Su Hao
通讯作者：
Lo, Su Hao