Extended Data Fig. 4: Transcriptional drug effects on the liver, eWAT and skeletal muscle.
From: GLP-1R–GIPR–PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice
a–l, DIO mice were treated once-daily via s.c. injections of GLP-1:GIP, GLP-1:GIP:Lani, Lani or vehicle for 12 days. 10 nmol kg−1. a,e,i, Venn-diagram with number of differentially expressed genes (DEGs; padj <0.05) in the liver (a), eWAT (e) and skeletal muscle (i). c,g,k, Principal component analysis (PCA) showing the first two principal components of overall gene expression in liver (c), eWAT (g) and skeletal muscle (k). b,f,j, Heatmap showing gene expression z-scores of all significantly up- or down-regulated genes for each treatment relative to vehicle in the liver (b), eWAT (f) and skeletal muscle (j). d,h,l, Gene expression overrepresentation analysis (ORA) of hallmark pathways in GLP-1:GIP:Lani–treated mice vs. vehicle, showing odds ratio, false discovery rate (FDR)–adjusted p-value, and enrichment score for each pathway in the liver (d), eWAT (h) and skeletal muscle (l). Data were analysed using two-sided Wald test with Benjamin-Hochburg FDR adjustment (a,b,e,f,h,i,j) or one-sided Fischer’s exact test with Benjamin-Hochburg FDR adjustment (d,l). Data in panel a–h comprise n = 8 mice each group; data in panel j–k comprise n = 7 mice for Vhcl and n = 8 for all other groups. Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001. Exact P-values, n-values and detailed statistics are provided in Supplementary Tables 1 and 3 and the Data Source File.
