MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity.
MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity.
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作者：
Xie H;Lim B;Lodish HF
我们研究了 microRNA (miRNA) 在脂肪细胞发育和肥胖中的调节和参与。使用 miRNA 微阵列，我们分析了前脂肪细胞 3T3-L1 细胞和来自瘦素缺陷 ob/ob 和饮食诱导的肥胖小鼠的脂肪细胞的脂肪形成过程中超过 370 个 miRNA 的表达。通过 RT-PCR 验证了关键 miRNA 的变化。我们进一步评估了肥胖脂肪组织中慢性炎症环境对脂肪细胞肿瘤坏死因子 (TNF)-α 治疗引起的 miRNA 表达失调的影响。我们通过功能获得方法对两种富含脂肪细胞的 miRNA miR-103 和 miR-143 进行了功能表征。类似的 miRNA 在体外和体内脂肪形成过程中受到不同的调节。重要的是，在脂肪生成过程中诱导的 miRNA 在两种类型肥胖小鼠的脂肪细胞中均下调，反之亦然。这些变化可能与慢性炎症环境有关，因为它们是通过分化脂肪细胞的 TNF-α 治疗来模拟的。前脂肪细胞中 miR-103 或 miR-143 的异位表达加速了脂肪生成，通过许多脂肪生成标记物的上调和脂肪生成早期阶段甘油三酯积累的增加来测量。我们的结果为 miR-103 在脂肪生物学中的功能提供了第一个实验证据。许多 miRNA 在脂肪生成和肥胖过程中显着的反向调节模式对于理解肥胖小鼠和人类的脂肪组织功能障碍以及慢性炎症和肥胖与胰岛素抵抗之间的联系具有重要意义。
We investigated the regulation and involvement of microRNAs (miRNAs) in fat cell development and obesity. Using miRNA microarrays, we profiled the expression of >370 miRNAs during adipogenesis of preadipocyte 3T3-L1 cells and adipocytes from leptin deficient ob/ob and diet-induced obese mice. Changes in key miRNAs were validated by RT-PCR. We further assessed the contribution of the chronic inflammatory environment in obese adipose tissue to the dysregulated miRNA expression by tumor necrosis factor (TNF)-α treatment of adipocytes. We functionally characterized two adipocyte-enriched miRNAs, miR-103 and miR-143, by a gain-of-function approach. Similar miRNAs were differentially regulated during in vitro and in vivo adipogenesis. Importantly, miRNAs that were induced during adipogenesis were downregulated in adipocytes from both types of obese mice and vice versa. These changes are likely associated with the chronic inflammatory environment, since they were mimicked by TNF-α treatment of differentiated adipocytes. Ectopic expression of miR-103 or miR-143 in preadipocytes accelerated adipogenesis, as measured both by the upregulation of many adipogenesis markers and by an increase in triglyceride accumulation at an early stage of adipogenesis. Our results provide the first experimental evidence for miR-103 function in adipose biology. The remarkable inverse regulatory pattern for many miRNAs during adipogenesis and obesity has important implications for understanding adipose tissue dysfunction in obese mice and humans and the link between chronic inflammation and obesity with insulin resistance.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
12.3
作者：
Hackl H;Burkard TR;Sturn A;Rubio R;Schleiffer A;Tian S;Quackenbush J;Eisenhaber F;Trajanoski Z
通讯作者：
Trajanoski Z
影响因子：
30.8
作者：
Krek, A;Grun, D;Rajewsky, N
通讯作者：
Rajewsky, N
影响因子：
29
作者：
Esau, C;Davis, S;Monia, BP
通讯作者：
Monia, BP
影响因子：
4.5
作者：
Kajimoto, Kazuaki;Naraba, Hiroaki;Iwai, Naoharu
通讯作者：
Iwai, Naoharu