白色脂肪组织以脂肪的形式储存多余的热量，以便可以在禁食期间供其他器官利用。哺乳动物也有少量的棕色脂肪组织，这主要是用于有效脂肪燃烧，用于产生热量。现在，南丹麦大学研究人员已经发现人体白色脂肪细胞被重新编程成为棕色脂肪细胞的机制。

白色脂肪组织褐变会增加身体能量的消耗，因此，或是肥胖症未来治疗的潜在策略。但面临的挑战是要重新编程白色脂肪组织中存储能量的白色脂肪细胞转化为所谓的“Brite”(白-棕色)脂肪细胞，从而使脂肪组织燃烧存储的多余能量。

在褐变过程中，研究人员采用了先进的基因组测序技术，已经调查了白色脂肪细胞的基因组如何被重新编程。我们用治疗II型糖尿病的药物刺激人体白色脂肪细胞褐变，并与白脂肪细胞比较，结果发现“Brite”(白-棕色)脂肪细胞有不同的基因程序，当处于激活的状态时，这些细胞能消耗能量。

通过识别那些直接参与重编程的基因组区域，研究人员也确定了在这个过程中的一个重要因素即基因调节蛋白KLF11(Kruppel样因子-11)，这是在所有的脂肪细胞中发现的蛋白，并且我们已经表明它对于重新编程发生是必需的。
原文标题：Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

原文摘要：Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ “superenhancers” that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program.

作者：阳光森林 点击：次