期刊
MOLECULAR METABOLISM
卷 11, 期 -, 页码 1-17出版社
ELSEVIER
DOI: 10.1016/j.molmet.2018.02.013
关键词
Obesity; Xbp1; ER stress; UPR; Pyrimidine; Uridine; CAD
资金
- American Diabetes Association [7-08-MN-53]
- American Heart Association [14SDG18440002, 14SFRN20510023, 14SFRN20670003]
- NIH [R01-DK55758, R01-DK099110, P01-AG051459, P01-DK088761]
- Novo Nordisk Research Foundation
- National Institutes of Health [HL-120732, HL-128215, HL-126012]
- Fondation Leducq [11CVD04]
- Cancer Prevention and Research Institute of Texas [RP110486P3]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK099110, K99DK114498, P01DK088761] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG051459] Funding Source: NIH RePORTER
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. (C) 2018 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据