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Updated: Feb 13, 2026

Isolation and Culturing of Primary Murine Adipocytes from Lean and Obese Mice
Published on: January 24, 2025
Adipocyte Xbp1s overexpression drives uridine production and reduces obesity
Yingfeng Deng1, Zhao V Wang2, Ruth Gordillo1
1Touchstone Diabetes Center, Department of Internal Medicines, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
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.
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