Research Article

An adipo-biliary-uridine axis that regulates energy homeostasis

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Science  17 Mar 2017:
Vol. 355, Issue 6330, eaaf5375
DOI: 10.1126/science.aaf5375

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  • Uridine transporters in the adipo-biliary-uridine axis
    • Marçal Pastor-Anglada, Professor of Biochemistry and Molecular Biology, University of Barcelona, IBUB, & CIBER EHD

    Deng et al. (Science 355, 1173, 2017) described the role uridine plays on thermoregulation and glucose sensitivity. The suggestion that an adipo-biliary-uridine axis is behind this novel physiological regulatory mechanism is particularly exciting. These authors discuss about how uridine is transported in this system, focusing on hepatocytes and bile tract and cite several studies from our laboratory. In order to make some points clearer I would like to comment on this topic. The authors mention that whereas CNT1- and CNT2-related proteins are responsible for the concentrative Na-dependent high-affinity transport of pyrimidine, less is known about the transport of uridine. In fact, whereas CNT1 is a pyrimidine nucleoside transporter, CNT2 is a purine-preferring nucleoside transporter, exceptionally translocating uridine despite being a pyrimidine. And this is indeed the case for the whole set of plasma membrane nucleoside transporter proteins (CNT1, CNT2, CNT3, ENT1, ENT2), because they all bind and translocate uridine although with different affinity (1). Thus, the major players in uridine uptake by cells are well known. They also mention that their data suggest the presence of nucleoside carriers on both canalicular and sinusoidal membranes of hepatocytes. Indeed, the polarized distribution of nucleoside transporters in hepatocytes is also known and reflects quite an atypical pattern for an epithelial cell, expressing CNT1 and CNT2 at both membrane domains(2). Evidence su...

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    Competing Interests: None declared.