title: An adipo-biliary-uridine axis that regulates energy homeostasis.
abstract: Uridine, a pyrimidine nucleoside present at high levels in the plasma of rodents and humans, is critical for RNA synthesis, glycogen deposition, and many other essential cellular processes. It also contributes to systemic metabolism, but the underlying mechanisms remain unclear. We found that plasma uridine levels are regulated by fasting and refeeding in mice, rats, and humans. Fasting increases plasma uridine levels, and this increase relies largely on adipocytes. In contrast, refeeding reduces plasma uridine levels through biliary clearance. Elevation of plasma uridine is required for the drop in body temperature that occurs during fasting. Further, feeding-induced clearance of plasma uridine improves glucose metabolism. We also present findings that implicate leptin signaling in uridine homeostasis and consequent metabolic control and thermoregulation. Our results indicate that plasma uridine governs energy homeostasis and thermoregulation in a mechanism involving adipocyte-dependent uridine biosynthesis and leptin signaling.
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Yingfeng
authors.identifier: 0000-0003-1314-5105
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Zhao V
authors.identifier: 0000-0002-9904-9538
authors.initials: ZV
authors.lastname: Wang
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ruth
authors.identifier: 0000-0001-6533-2493
authors.initials: R
authors.lastname: Gordillo
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Yu
authors.identifier: 0000-0002-9678-3382
authors.initials: Y
authors.lastname: An
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Qiren
authors.identifier: 0000-0002-1131-3120
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jun
authors.identifier: 0000-0001-9833-4356
authors.initials: J
authors.lastname: Yoshino
authors.affiliation: Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kelly M
authors.identifier: 0000-0003-4434-2814
authors.initials: KM
authors.lastname: Cautivo
authors.affiliation: Department of Biochemistry and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Jef
authors.identifier: 0000-0001-8816-5798
authors.initials: J
authors.lastname: De Brabander
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.affiliation: Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Horton
authors.affiliation: Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.|Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Joseph A
authors.identifier: 0000-0002-5379-1614
authors.initials: JA
authors.lastname: Hill
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Samuel
authors.identifier: 0000-0001-7127-1156
authors.initials: S
authors.lastname: Klein
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. philipp.scherer@utsouthwestern.edu.
authors.forename: Philipp E
authors.identifier: 0000-0003-0680-3392
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation; D004734:Energy Metabolism; D005215:Fasting / Q000378:metabolism*; D065669:Hepatobiliary Elimination; D006801:Humans; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014529:Uridine / Q000096:biosynthesis* / Q000097:blood*
chemical_list: D001786:Blood Glucose; D020738:Leptin; D014529:Uridine