Fig. 3: Genetic depletion of ACBP/DBI prevents Cushing’s syndrome.
From: Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing’s syndrome
a, A schematic representation of the different C57BL/6J lineages conditionally knocked out for the ACBP/DBI protein. The conditional knockout of Acbp/Dbi was achieved by administering repeated i.p. injections of tamoxifen (TAM) to mice with a floxed Acbp/Dbi gene (genotype: Dbifl/fl), combined with either a latent ubiquitous CRE recombinase (UBC-cre+) or a hepatocyte-specific CRE recombinase (TTR-cre+). b–o, Female Dbi−/− mice and their wild-type controls (Dbi+/+) as well as female liver-Dbi−/− mice and their wild-type controls (liver-Dbi+/+) were treated with CORT (100 μg ml−1) or vehicle (control) in drinking water (p.o.) for 5 weeks: Plasma ACBP was quantified by ELISA (n = 6 per group) (b and k), and hepatic Acbp mRNA was assessed by qRT–PCR (n = 6 per group) (c and l); average food intake (n = 3 cages per group) (d and m) and body weight (n = 8 and 6 mice per group) (e and n) were monitored in the indicated groups (the P value represents the comparison of areas under the curve); the heatmap shows the standardized deviations (z scores) of tissue weights relative to body weight and the quantification of various biochemical parameters across the treatment groups (n = 6 mice per group) (f and o) (statistical comparisons were performed by pairwise (two-tailed) Wilcoxon test with false discovery rate (FDR) correction for multiple comparisons; P values are indicated); GTT (n = 6 mice per group) (g) and ITT (n = 6 mice per group) (i) were monitored in the indicated groups (the P value represents the comparison of areas under the curve; h and j). Statistical comparisons were performed by pairwise Wilcoxon test with FDR correction for multiple comparisons in the heatmaps (P values are indicated). All dot plots depict mean ± s.e.m. Two independently repeated experiments were conducted; only one representative result is shown. The curves in d, e, m and n were longitudinally analysed with type II ANOVA and pairwise comparisons. The data in b, c, h and j–l were analysed using one-way ANOVA with Tukey correction. vWAT, visceral white adipose tissue; iWAT, inguinal white adipose tissue; pWAT, perigonadal white adipose tissue; iBAT, interscapular brown adipose tissue; ND, not detectable. Created with BioRender.com.
