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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 29.0 ) Pub Date : 2017-11-16 00:00:00 , DOI: 10.1016/j.cmet.2017.10.008
Joan Sanchez-Gurmaches,Yuefeng Tang,Naja Zenius Jespersen,Martina Wallace,Camila Martinez Calejman,Sharvari Gujja,Huawei Li,Yvonne J.K. Edwards,Christian Wolfrum,Christian M. Metallo,Søren Nielsen,Camilla Scheele,David A. Guertin

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 anabolicde novolipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates withUcp1expression. 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,从而优化燃料存储和生热作用。

棕色脂肪组织(BAT)是代谢疾病的治疗靶标;因此,了解其代谢途径在临床上很重要。BAT的许多研究都将啮齿类动物的轻度与严寒相比较。在这里,我们比较了热中性小鼠和轻度适应性小鼠之间的BAT重塑,这些条件与人类更为相关。尽管BAT因分解代谢的β-氧化能力而闻名,但我们反常地发现,编码ACLY,ACSS2,ACC和FASN的合成代谢新脂肪生成(DNL)基因在轻度感冒中最上调,而在人类中,DNL与Ucp1表达相关。脂肪细胞DNL的调节和功能及其与生热的关系尚不清楚。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,而寒冷会在BAT中诱导AKT2-ChREBP途径来优化燃料储存和生热作用。这些数据提供了对脂肪细胞DNL调节和功能的深入了解,并说明了生热作用的代谢灵活性。
更新日期:2017-11-19
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