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Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis.
Cell Metabolism ( IF 27.7 ) Pub Date : 2018-Jan-09 , DOI: 10.1016/j.cmet.2017.10.008 Joan Sanchez-Gurmaches 1 , Yuefeng Tang 1 , Naja Zenius Jespersen 2 , Martina Wallace 3 , Camila Martinez Calejman 1 , Sharvari Gujja 1 , Huawei Li 1 , Yvonne J K Edwards 1 , Christian Wolfrum 4 , Christian M Metallo 3 , Søren Nielsen 5 , Camilla Scheele 2 , David A Guertin 1
Cell Metabolism ( IF 27.7 ) Pub Date : 2018-Jan-09 , DOI: 10.1016/j.cmet.2017.10.008 Joan Sanchez-Gurmaches 1 , Yuefeng Tang 1 , Naja Zenius Jespersen 2 , Martina Wallace 3 , Camila Martinez Calejman 1 , Sharvari Gujja 1 , Huawei Li 1 , Yvonne J K Edwards 1 , Christian Wolfrum 4 , Christian M Metallo 3 , Søren Nielsen 5 , Camilla Scheele 2 , David A Guertin 1
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Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis.
中文翻译:
棕色脂肪 AKT2 是一种冷诱导激酶,可刺激 ChREBP 介导的从头脂肪生成,以优化燃料储存和产热。
棕色脂肪组织(BAT)是代谢性疾病的治疗靶点;因此,了解其代谢回路在临床上很重要。许多 BAT 研究对轻度寒冷和重度寒冷的啮齿动物进行了比较。在这里,我们比较了热中性小鼠和轻度寒冷适应小鼠之间的 BAT 重塑,这些条件与人类更相关。尽管 BAT 以分解代谢 β-氧化能力而闻名,但矛盾的是,我们发现编码 ACLY、ACSS2、ACC 和 FASN 的合成代谢从头脂肪生成 (DNL) 基因是受轻度寒冷影响最上调的基因之一,而且在人类中,DNL 与Ucp1 表达。脂肪细胞 DNL 的调节和功能及其与产热的关系尚不清楚。我们提供的证据表明 AKT2 通过刺激 ChREBPβ 转录活性来驱动脂肪细胞中的 DNL,并且寒冷会诱导 BAT 中的 AKT2-ChREBP 通路以优化燃料储存和产热。这些数据提供了对脂肪细胞 DNL 调节和功能的深入了解,并说明了产热的代谢灵活性。
更新日期:2018-02-02
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
棕色脂肪 AKT2 是一种冷诱导激酶,可刺激 ChREBP 介导的从头脂肪生成,以优化燃料储存和产热。
棕色脂肪组织(BAT)是代谢性疾病的治疗靶点;因此,了解其代谢回路在临床上很重要。许多 BAT 研究对轻度寒冷和重度寒冷的啮齿动物进行了比较。在这里,我们比较了热中性小鼠和轻度寒冷适应小鼠之间的 BAT 重塑,这些条件与人类更相关。尽管 BAT 以分解代谢 β-氧化能力而闻名,但矛盾的是,我们发现编码 ACLY、ACSS2、ACC 和 FASN 的合成代谢从头脂肪生成 (DNL) 基因是受轻度寒冷影响最上调的基因之一,而且在人类中,DNL 与Ucp1 表达。脂肪细胞 DNL 的调节和功能及其与产热的关系尚不清楚。我们提供的证据表明 AKT2 通过刺激 ChREBPβ 转录活性来驱动脂肪细胞中的 DNL,并且寒冷会诱导 BAT 中的 AKT2-ChREBP 通路以优化燃料储存和产热。这些数据提供了对脂肪细胞 DNL 调节和功能的深入了解,并说明了产热的代谢灵活性。