Analysis of in vitro insulin-resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance.
Analysis of in vitro insulin-resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance.
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DOI：
10.1016/j.celrep.2013.08.039
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发表时间：
2013-10-17
期刊：
影响因子：
8.8
通讯作者：
Fraenkel E
中科院分区：
文献类型：
--
作者：
Lo KA;Labadorf A;Kennedy NJ;Han MS;Yap YS;Matthews B;Xin X;Sun L;Davis RJ;Lodish HF;Fraenkel E
饮食引起的肥胖使个体易患胰岛素抵抗，脂肪组织在该疾病中起主要作用。胰岛素抵抗可以通过各种治疗在培养的脂肪细胞中诱导，但是这些模型捕获体内反应的哪些方面是未知的。我们使用全局RNA测序（RNA-Seq）研究TNFα、缺氧、地塞米松、高胰岛素以及TNFα和缺氧联合诱导的变化，并将结果与饮食诱导肥胖（DIO）小鼠白色脂肪组织的变化进行比较。我们发现，不同的体外模型捕捉DIO脂肪胰岛素抵抗的不同特征，并且TNFα和缺氧的组合治疗最能够模拟体内变化。利用全基因组DNA酶I超敏反应测序（DNase-Seq）技术，我们进一步研究了TNFα诱导的胰岛素抵抗的转录调控，发现C/EPBβ是脂肪胰岛素抵抗的潜在关键调控因子。
Diet-induced obesity predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but it is unknown what aspects of the in vivo responses are captured by these models. We use global RNA-sequencing (RNA-Seq) to investigate changes induced by TNFα, hypoxia, dexamethasone, high insulin, and a combination of TNFα and hypoxia, comparing the results to the changes in white adipose tissue from diet-induced obese (DIO) mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNFα and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing (DNase-Seq), we further examined the transcriptional regulation of TNFα-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance.
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29
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影响因子：
4.8
作者：
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通讯作者：
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