Extended Data Fig. 8. Schematic representation of inosine production, clearance and action in thermogenic adipocytes.

ATP and ADP are degraded by ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) to AMP, which in turn is metabolized to adenosine by ecto 5’-nucleotidase (NT5E). Inosine is generated by adenosine deaminase (ADA) or is released into the interstitial space via ENT1. Inosine signaling is terminated by either uptake of inosine into the cell by ENT1 or degradation by purine nucleoside phosphorylase (PNP). Extracellular inosine exerts its effects via the purinergic P1 receptors A_2A and A_2B resulting in G_s protein-induced cAMP production. Parts of the figure were drawn by using pictures from Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (https://creativecommons.org/licenses/by/3.0/).