Fig. 6: Cotadutide increases brown adipose tissue mitochondrial activity and content.

Transcriptomic and histological analyses of brown adipose tissue (BAT) following 28-day treatment of cotadutide (10 nmol/kg, blue triangles), compared to vehicle (red circles). Volcano plot of genes significantly up- (red) or down-regulated (blue) by cotadutide in BAT as identified via RNA-seq. Vehicle (n = 4); Cotadutide (n = 5) mice per group (A). Gene ontology analysis for enriched biological process (red), molecular function (orange), or cellular component (yellow) for genes significantly upregulated by cotadutide in BAT (B). Representative images of immunohistochemical staining of BAT for UCP-1 (C) and H&E (D) of vehicle (top) and cotadutide (bottom). Vehicle (n = 8); Cotadutide (n = 7) mice per group. Quantification of BAT Score from H&E staining (E) Vehicle (n = 8); Cotadutide (n = 7) mice per group. Quantification of histological parameters from electron microscopy imaging in J, including lipid droplet area (F), lipid droplet size (G), mitochondria area (H), and mitochondria size (I). Biologic replicates are n = 2 mice per group. Technical replicates are vehicle (n = 10) and cotadutide (n = 19) images per mouse. Representative images of electron microscopy imaging of vehicle (left) and cotadutide (right) BAT (J). Adjustments were made for multiple comparisons using the Benjamini–Hochberg adjustment. Genes with Benjamini–Hochberg false discovery rate <0.05 as determined by DESeq2 were considered significant (A) two-sided Student’s t-test (E–I). Data shown as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < .0001. Exact p values are included in the Source Data file. Source data are provided as a Source Data file.