Fig. 4: Adipose GPR81 is the major mediator of pro-catabolic effects of lactate.
From: Activation of GPR81 by lactate drives tumour-induced cachexia
a, Lactate levels of the interstitial fluid of iWAT from KrasLSL-G12D/+;p53R172H/+ mice after intranasal administration of control adenovirus (n = 5) or adenovirus expressing Cre recombinase (n = 4). b, Linear regression analysis showing the correlation between iWAT weights and lactate levels of the iWAT interstitial fluid from KrasLSL-G12D/+;p53R172H/+ mice after intranasal administration of adenovirus (n = 9). c, Change in the body fat percentage in the WT tumour-free (WT control, n = 15), WT TB (n = 14), GPR81 knockout tumour-free (GPR81−/− control, n = 12) and GPR81−/− TB (n = 15) mice determined by magnetic resonance imaging. d, Representative western blot and statistical data showing GPR81 protein levels in the iWAT isolated from GPR81fl/fl and GPR81fl/flAdipoqcre mice (n = 4 for each group). e–g, Blood lactate levels (e), body weight change (f) and tissue weights (g) in the tumour-free (control) GPR81fl/fl and GPR81fl/flAdipoqcre mice or implanted with LLC cells (TB) for 24 days (n = 10 for each group). h, Representative images of H&E staining and immunofluorescence staining of UCP1 in the iWAT from GPR81fl/fl and GPR81fl/flAdipoqcre mice with or without LLC tumour (n = 5 for each group). Scale bars, 100 μm. i, Statistical results of the immunofluorescence signal intensity of UCP1 in the iWAT from GPR81fl/fl and GPR81fl/flAdipoqcre mice with or without LLC tumour (n = 8 for each group). j, Statistical results showing the distribution of adipocyte sizes in the iWAT from GPR81fl/fl and GPR81fl/flAdipoqcre mice with or without tumour (n = 5 for each group). k, Representative images of H&E staining of skeletal muscle from GPR81fl/fl and GPR81fl/flAdipoqcre mice with or without tumour (n = 5 for each group). Scale bars, 100 μm. All data are presented as the mean ± s.e.m. P values were determined by two-tailed unpaired Student’s t-test (a and d), two-way ANOVA (c and j) and one-way ANOVA (e–g and i). P value of the correlation was determined by two-tailed Pearson correlation analysis (b).
