| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 11, Iss , Pp 1-17 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2018.02.013 |
| Popis: |
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 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
