Year: 2018
Type: article
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.
Source: Molecular Metabolism
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,270
Funders: American Diabetes Association, American Heart Association, Cancer Prevention and Research Institute of Texas, University of Texas Southwestern Medical Center, Novo Nordisk UK Research Foundation, Fondation Leducq, Novo Nordisk, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1802610678, G2123367144, G3479406049, G3736404961, G3996049474, Gap Junction Dependent and Independent Roles of Connexin43 in Metabolic Tissues, G4832285854, G5294443024, G561344009, G573276430, G5983394923, Adiponectin, A Protein Secreted From Adipose Tissue, G6478088963, G8070748056, G837859629, G874363986, P3: Maladaptive cardiomyocyte autophagy as a mechanism of doxorubicin-induced heart failure, G9000022988, G9000089780, G9000103934, G9000136235, G9000171943, G9000192291, G9000274628, Competing Renewal P01
OpenAlex ID: W2789448281