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. 2021 Dec 8;12:7144. doi: 10.1038/s41467-021-27442-x

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© The Author(s) 2021

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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Fig. 7 — a Expression of GPR180 in WAT of normal weight men and individuals with obesity and normal glucose tolerance (NGT), obesity with prediabetes and obesity with diabetes (n = 57; p = 0.0021 for individuals with obesity and NGT, p = 0.0003 for individuals with obesity and prediabetes and p = 0.0013 for patients with obesity and diabetes). b Expression of GPR180 in paired samples of SAT and isolated adipocytes (n = 21; p = 0.0077). Correlation of adipocyte GPR180 level with c adipocyte size (n = 54), d suppression of fatty acid release during EHC (n = 55) and e resting energy expenditure (n = 31). f Incidence of circulating CTHRC1 in normal weight individuals, and patients affected by obesitybut NGT, patients having obesity and prediabetes and/or type 2 diabetes (n = 85; p = 0.02533) and its association with g basal energy expenditure and h energy expenditure measured during the steady state of EHC (n = 20). i Schematic illustration of the signalling mechanism identified in this study. Data are shown as mean ± SEM. Statistical analysis was performed by one-way ANOVA with Dunett post-hoc test (a), paired Student´s t-test (b) or Fisher´s exact test (f). For association of GPR180 expression in WAT or circulating CTHRC1 with metabolic parameters Pearson’s correlation coefficient was calculated (c–e, g, h). Significant differences are indicated as *p < 0.05, **p < 0.01 and ***p < 0.001. CTHRC1 Collagen triple helix repeat containing 1, EHC euglycaemic hyperinsulinaemic clamp, FFA free fatty acids, GPR180 G protein-coupled receptor 180, REE resting energy expenditure, SAT subcutaneous adipose tissue, SMAD3 Mothers against decapentaplegic homolog 3, TGFβ1 Transforming growth factor β1, TGFβR1 Transforming growth factor β receptor type 1, TGFβR2 Transforming growth factor β receptor type 2, UCP1 Uncoupling protein 1.