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Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.

Publication ,  Journal Article
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
Published in: Mol Metab
May 2018
Published version (DOI) Link to item

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.

Duke Scholars

Rana K. Gupta
Author Rana K. Gupta Medicine, Endocrinology, Metabolism, and Nutrition
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Published In

Mol Metab

DOI

10.1016/j.molmet.2018.02.013

EISSN

2212-8778

Publication Date

May 2018

Volume

11

Start / End Page

1 / 17

Location

Germany

Related Subject Headings

  • X-Box Binding Protein 1
  • Uridine
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipolysis
  • Cells, Cultured
  • Animals
  • Adipocytes
 

Citation

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ICMJE
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Deng, Y., Wang, Z. V., Gordillo, R., Zhu, Y., Ali, A., Zhang, C., … Scherer, P. E. (2018). Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Mol Metab, 11, 1–17. https://doi.org/10.1016/j.molmet.2018.02.013
Deng, Yingfeng, Zhao V. Wang, Ruth Gordillo, Yi Zhu, Aktar Ali, Chen Zhang, Xiaoding Wang, et al. “Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.” Mol Metab 11 (May 2018): 1–17. https://doi.org/10.1016/j.molmet.2018.02.013.
Deng Y, Wang ZV, Gordillo R, Zhu Y, Ali A, Zhang C, et al. Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Mol Metab. 2018 May;11:1–17.
Deng, Yingfeng, et al. “Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.” Mol Metab, vol. 11, May 2018, pp. 1–17. Pubmed, doi:10.1016/j.molmet.2018.02.013.
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. Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Mol Metab. 2018 May;11:1–17.
Journal cover image

Published In

Mol Metab

DOI

10.1016/j.molmet.2018.02.013

EISSN

2212-8778

Publication Date

May 2018

Volume

11

Start / End Page

1 / 17

Location

Germany

Related Subject Headings

  • X-Box Binding Protein 1
  • Uridine
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipolysis
  • Cells, Cultured
  • Animals
  • Adipocytes