Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.
Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.
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DOI：
10.1016/j.molmet.2018.02.013
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发表时间：
2018-05
影响因子：
8.1
通讯作者：
Scherer PE
中科院分区：
文献类型：
--
作者：
Deng Y;Wang ZV;Gordillo R;Zhu Y;Ali A;Zhang C;Wang X;Shao M;Zhang Z;Iyengar P;Gupta RK;Horton JD;Hill JA;Scherer PE
剪接转录因子Xbp1（Xbp1s）是未折叠蛋白反应（UPR）的一种转导因子，调节脂解。当脂肪细胞中尿苷合成也被激活时，禁食刺激脂解。在这里，我们研究了调节作用Xbp1s在刺激尿苷合成脂肪细胞和甘油三酯动员诱导小鼠模型。Xbp1s是脂肪细胞尿苷合成和释放的关键分子，通过激活氨甲酰磷酸合成酶2、天冬氨酸转氨甲酰酶、二氢乳清酸酶（CAD）（UMP生物合成的限速酶）来参与。脂肪细胞Xbp1s过表达驱动能量动员并通过激活嘧啶生物合成途径保护小鼠免于肥胖这些观察结果表明，Xbp1s是脂肪细胞中尿苷产生的有效刺激剂，通过诱导无效的生物合成循环来增强脂解并引发潜在的抗肥胖策略。内质网应激是肥胖相关代谢紊乱的重要机制。Xbp1s是内质网应激反应的关键转导子，刺激尿苷的生物合成。脂肪细胞合成的尿苷对血浆尿苷供应至关重要。Xbp1s刺激脂肪细胞尿苷合成促进体重减轻
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. ER stress is a key mechanism of obesity-related metabolic disorders. Xbp1s, a key transducer of ER stress response, stimulates uridine biosynthesis. Uridine synthesized in adipocytes is critical for plasma uridine supply. Stimulation of uridine synthesis in adipocyte by Xbp1s promotes weight loss.
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影响因子：
2.1
作者：
Morris, AD;Cordi, AA
通讯作者：
Cordi, AA
DOI：
10.1098/rstb.1995.0008
发表时间：
1995-01-30
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
SMITH, KA;AGARWAL, ML;STARK, GR
通讯作者：
STARK, GR
影响因子：
5.3
作者：
Bogdanovic E;Kraus N;Patsouris D;Diao L;Wang V;Abdullahi A;Jeschke MG
通讯作者：
Jeschke MG
影响因子：
64.8
作者：
Reimold, AM;Iwakoshi, NN;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH