adipocyte xbp1s overexpression drives uridine production and reduces obesity

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ID: 255851
2018
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Abstract
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. Results: 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. Keywords: Obesity, Xbp1, ER stress, UPR, Pyrimidine, Uridine, CAD
Reference Key
deng2018molecularadipocyte Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Yingfeng Deng;Zhao V. Wang;Ruth Gordillo;Yi Zhu;Aktar Ali;Chen Zhang;Xiaoding Wang;Mengle Shao;Zhuzhen Zhang;Puneeth Iyengar;Rana K. Gupta;Jay D. Horton;Joseph A. Hill;Philipp E. Scherer
Journal Small (Weinheim an der Bergstrasse, Germany)
Year 2018
DOI
DOI not found
URL
http://www.sciencedirect.com/science/article/pii/S2212877818301868
Keywords
internal medicine

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