Fig. 6: The Ucp1-mediated thermogenic pathway is activated in AA005-treated mice and Hadha^ΔAdipo mice.

a Heatmap generated by RNA-seq analysis displaying differentially regulated genes between AA005-treated and Hadha^ΔAdipo mice fed HFD in iWAT (n = 5). Red and blue colors indicate upregulated or downregulated genes. b Significant enrichment in KEGG terms. Bars indicate the number or proportions of genes within each functional class, ranked based on protein coverage. c Heatmap showing the mean fold-change of the indicated metabolic processes in vehicle control, AA005-treated and Hadha^ΔAdipo mice fed HFD. Red and blue colors indicated upregulated or downregulated genes. d Hadha as the central node in the network of gene interactions with thermogenesis pathways. The protein expression and quantification analysis of UCP1, p-PKA, and p-HSL in BAT tissue derived from vehicle- or AA005-treated mice fed HFD for 22 weeks (e), as well as Hadha^fl/fl or Hadha^ΔAdipo mice fed HFD for 18 weeks (f) (n = 3). Actin was used as the loading control. g–l Vehicle- or AA005-treated mice fed CD subjected to cold room stress before analysis. Rectal temperature of vehicle- or AA005-treated mice (4 °C acute cold in (g) programmed cooling to 6 °C chronic cold in (j), n = 5 per group). Representative western blot and quantification of UCP1 and PKA activation in the BAT (acute cold in (i), chronic cold in (l)) (n = 3). Representative images of haematoxylin and eosin (H&E) stained of iWAT and BAT (acute cold in (h), iWAT, n = 248 (vehicle) and 301 (AA005) adipocytes per group; BAT, n = 287 (vehicle) and 193 (AA005) LDs per group, chronic cold in (k), iWAT, n = 100 (vehicle) and 309 (AA005) adipocytes per group; BAT, n = 600 (vehicle) and 478 (AA005) LDs per group; Scale bar, 50 μm. Data are presented as mean ± SEM. Unpaired, two-tailed Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001). Source data are provided as a Source Data file.