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. 2022 Jul 5;609(7926):361–368. doi: 10.1038/s41586-022-05041-0

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — a, b Heatmap of top 25 secreted metabolites of untargeted metabolomics of human BA: (a) treated with and without nutlin-3 (b) irradiated with UV, upregulated metabolites are shown in red, downregulated metabolites are shown in blue (n = 6). c, Concentrations of purinergic molecules in the supernatant of human BA treated with and without nutlin-3 (n = 6). d, Extracellular inosine concentrations of human BA treated with and without NE (n = 6). e, Representative Western Blot and quantification for ENT1 knockdown in human BA induced by different lentiviral Crispr-Cas9 vectors (CRISPR1, 2, 3) in comparison to a control vector (NTC2B) and to not-transduced (Control) cells (n = 3). Calnexin serves as a loading control. For gel source data see Supplementary Information. f, extracellular inosine concentrations in human BA with (ENT1-Crispr) and without (NTC2B) ENT1 knockdown treated with and without Dipyridamole (Dip) (1µM) (n = 4-6). g, mRNA expression of adipogenic (PPARG) and thermogenic (PRDM16, TFAM, UCP1, PPARGC1A) marker genes in human BA with (ENT1-Crispr) and without (NTC2B) ENT1 knockdown (n = 5-6). h, Expression of the purinergic enzymes ENTPD1, NT5E, ADA, PNP and XO in human brown (hBA) and white (hWA) adipocytes (n = 5-6). i, Basal oxygen consumption rate (OCR) of hWA with (ENT1-Crispr) and without (NTC2B) ENT1 knockdown (n = 4). j, k Linear regression of SLC29A1 and (j) PPARGC1A expression (n = 1,476; ρSpearman = −0.71) and PRDM16 expression (n = 1,476; ρSpearman = −0.64) in human subcutaneous WAT (SC) and (k) PPARGC1A expression (n = 1,583; ρSpearman = −0.6) and PRDM16 expression (n = 1,583; ρSpearman = −0.63) in human visceral WAT (VIS), p-values were corrected for multiple inference using the Holm method. For all: *p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.001. For exact p-values see Source Data. Data are represented as mean ± s.e.m. Two-tailed t-test was applied for c, d, g, h, i, One-way ANOVA with Tukey’s post hoc test for a, b, e, f.