Adipocyte Xbp1s overexpression drives uridine production and reduces obesity

作者：Deng, Yingfeng; Wang, Zhao, V; Gordillo, Ruth; Zhu, Yi; Ali, Aktar; Zhang, Chen; Wang, Xiaoding; Shao, Mengle; Zhang, Zhuzhen; Iyengar, Puneeth; Gupta, Rana K.; Horton, Jay D.; Hill, Joseph A.; Scherer, Philipp E.^*

来源：Molecular Metabolism, 2018, 11: 1-17.

DOI：10.1016/j.molmet.2018.02.013

• Obesity
• Xbp1
• ER stress
• UPR
• Pyrimidine
• Uridine
• CAD

Objective: 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.
Methods: Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models. R
esults: 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.
Conclusion: 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.

• 出版日期2018-5
• 单位武汉大学