Fig. 5: CTHRC1, an adipokine that requires GPR180 to enhance the beige adipocyte phenotype. | Nature Communications

Fig. 5: CTHRC1, an adipokine that requires GPR180 to enhance the beige adipocyte phenotype.

From: GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1

Fig. 5: CTHRC1, an adipokine that requires GPR180 to enhance the beige adipocyte phenotype.

a Representative blots and b quantification of CTHRC1 protein in human adipocytes (n = 4; p = 0.0011) and c cell-conditioned media (n = 7; p = 0.0408). d Expression of CTHRC1 in supraclavicular brown and subcutaneous white adipose tissue of 6 healthy volunteers with detectable BAT (p = 0.3008). Effect of long-term (72 h) CTHRC1 treatment on e UCP1 protein (n = 4; p = 0.0001 for 100 ng/ml and p = 0.0064 for 500 ng/ml) and f mitochondrial respiration (n = 5; basal p = 0.0102, cAMP-stimulated uncoupled p < 0.0001 for 100 ng/ml and p = 0.0021 for 500 ng/ml, maximal p = 0.0207) in mature human beige adipocytes. g Effect of long-term (72 h) CTHRC1 (500 ng/ml) and TGFβ1 (1 ng/ml) on mitochondrial respiration in beige hMADS cells in presence of IgG (control) and neutralizing anti-TGFβ antibody (1 μg/ml) (n = 6; basal CTHRC1 IgG p = 0.0376, CTHRC1 anti-TGFβ p = 0.0489, TGFβ IgG p = 0.0474; uncoupled CTHRC1 IgG p = 0.0372, CTHRC1 anti-TGFβ p = 0.0079; coupled TGFβ IgG p = 0.0449; cAMP-stimulated uncoupled CTHRC1 IgG p = 0.0407, CTHRC1 anti-TGFβ p = 0.0440, TGFβ IgG p = 0.0317; maximal CTHRC1 IgG p = 0.0478, CTHRC1 anti-TGFβ p = 0.0310). h UCP1 levels (n = 6; siGPR180 in PBS p = 0.0016, CTHRC1 in ctrl siRNA p < 0.0001 and siGPR180 in CTHRC1 treatment p < 0.0001) and i mitochondrial respiration (n = 10; p < 0.0001 basal, p < 0.0001 coupled, p = 0.0094 for CTHRC1 treatment in ctrl siRNA and p = 0.0013 for siGPR180 in PBS treated in cAMP-stimulated uncoupled respiration, p < 0.0001 maximal respiration) in adipocytes following long-term (72 h) CTHRC1 treatment (500 ng/ml) in combination with GPR180 knockdown. Effect of CTHRC1 silencing on (j) UCP1 protein (ctrl siRNA n = 8, siCTHRC1 n = 9; p = 0.0002) and k mitochondrial oxygen consumption (n = 5; p = 0.0311 for uncoupled respiration, p = 0.0326 for cAMP-stimulated uncoupled respiration) in hMADS cells. Data are shown as mean ± SEM. Statistical analysis was performed by unpaired Student´s t-test (b, c, j), paired Student´s t-test (d), one-way ANOVA with Dunett’s post-hoc-test (e) or two-way ANOVA with Sidak and Tukey post-hoc tests (f–i, k). Significance is indicated as *p < 0.05, **p < 0.01 and ***p < 0.001. cAMP cyclic adenosine monophosphate, CTHRC1 Collagen triple helix repeat containg 1, GPR180 G protein-coupled receptor 180, hMADS human multipotent adipose-derived stem cells, IgG imunoglobulin G, OCR oxygen consumption rate, PBS phosphate buffered saline, scBAT supraclavicular brown adipose tissue, TGFβ Transforming growth factor β, UCP1 Uncoupling protein 1, WAT white adipose tissue.

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