Touchstone Diabetes Center, Department of Internal Medicines, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Mol Metab. 2018 May;11:1-17. doi: 10.1016/j.molmet.2018.02.013. Epub 2018 Mar 2.
The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes.
Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models.
Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release by activation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), the rate-limiting enzyme for UMP biosynthesis. Adipocyte Xbp1s overexpression drives energy mobilization and protects mice from obesity through activation of the pyrimidine biosynthesis pathway.
These observations reveal that Xbp1s is a potent stimulator of uridine production in adipocytes, enhancing lipolysis and invoking a potential anti-obesity strategy through the induction of a futile biosynthetic cycle.
拼接转录因子 Xbp1（Xbp1s）是未折叠蛋白反应（UPR）的传感器，可调节脂肪分解。在脂肪细胞中尿嘧啶合成也被激活时，禁食会刺激脂肪分解。
在这里，我们使用可诱导的小鼠模型检查了 Xbp1s 在刺激脂肪细胞中尿嘧啶生物合成和甘油三酯动员中的调节作用。
Xbp1s 通过激活氨基甲酰磷酸合成酶 2、天冬氨酸转氨甲酰酶、二氢乳清酸酶（CAD），即 UMP 生物合成的限速酶，是参与脂肪细胞尿嘧啶生物合成和释放的关键分子。脂肪细胞 Xbp1s 的过表达通过激活嘧啶生物合成途径驱动能量动员，并通过激活无效生物合成循环保护小鼠免受肥胖。
这些观察结果表明，Xbp1s 是脂肪细胞中尿嘧啶产生的有效刺激物，通过诱导无效生物合成循环增强脂肪分解并提出一种潜在的抗肥胖策略。
Zotero 插件
