An adipo-biliary-uridine axis that regulates energy homeostasis

Yingfeng Deng, Zhao V. Wang, Ruth Gordillo, Yu An, Chen Zhang, Qiren Liang, Jun Yoshino, Kelly M. Cautivo, Jef De Brabander, Joel K. Elmquist, Jay D. Horton, Joseph A. Hill, Samuel Klein, Philipp E. Scherer

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37 Scopus citations

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.

Original languageEnglish
Article numbereaaf5375
JournalScience
Volume355
Issue number6330
DOIs
StatePublished - Mar 17 2017

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    Deng, Y., Wang, Z. V., Gordillo, R., An, Y., Zhang, C., Liang, Q., Yoshino, J., Cautivo, K. M., De Brabander, J., Elmquist, J. K., Horton, J. D., Hill, J. A., Klein, S., & Scherer, P. E. (2017). An adipo-biliary-uridine axis that regulates energy homeostasis. Science, 355(6330), [eaaf5375]. https://doi.org/10.1126/science.aaf5375