Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2).
Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2).
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DOI：
10.2337/db12-1745
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发表时间：
2013-08
期刊：
影响因子：
7.7
通讯作者：
Crossley M
中科院分区：
文献类型：
--
作者：
Bell-Anderson KS;Funnell AP;Williams H;Mat Jusoh H;Scully T;Lim WF;Burdach JG;Mak KS;Knights AJ;Hoy AJ;Nicholas HR;Sainsbury A;Turner N;Pearson RC;Crossley M
Krüppel样因子3（KLF 3）是一种转录调节因子，我们已经证明其参与体外脂肪形成的调节。在这里，我们报告说，KLF 3基因敲除小鼠是瘦的，并防止饮食诱导的肥胖和葡萄糖耐受不良。在普通饮食中，血浆瘦素水平降低，脂联素水平升高。尽管体重和肥胖显著降低，野生型和基因敲除动物显示出相等的能量摄入、消耗和排泄。为了研究这些观察结果背后的分子事件，我们使用微阵列分析来比较Klf 3 +/+和Klf 3 −/−组织中的基因表达。我们发现，Fam 132 a的mRNA表达，它编码一个新发现的胰岛素增敏脂肪因子，adipolin，是显着上调KLF 3的情况下。我们证实，KLF 3结合Fam 132 a启动子在体外和体内，这导致启动子活性的抑制。此外，与野生型同窝仔相比，Klf 3 −/−小鼠的血浆脂蛋白水平显著升高。通过靶向KLF 3提高adipolin水平为治疗胰岛素抵抗提供了一种新的潜在治疗策略。
Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3+/+ and Klf3−/− tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3−/− mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.
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DOI：
10.1073/pnas.0409177102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Neve, B;Fernandez-Zapico, ME;Froguel, P
通讯作者：
Froguel, P
影响因子：
12.4
作者：
Pei, H.;Yao, Y.;Wu, J-R
通讯作者：
Wu, J-R
影响因子：
4.8
作者：
Li, D;Yea, S;Walsh, MJ
通讯作者：
Walsh, MJ
影响因子：
5.3
作者：
Funnell, Alister P. W.;Maloney, Christopher A.;Crossley, Merlin
通讯作者：
Crossley, Merlin
影响因子：
4.8
作者：
Eaton, Sally A.;Funnell, Alister P. W.;Crossley, Merlin
通讯作者：
Crossley, Merlin