Fig. 6: Knockout of cGAS or STING in mice increased PKA signaling and thermogenesis.

Immunoblot analysis of UCP1 expression and the phosphorylation of PKA substrates including HSL in a iWAT and b BAT of STING^gt and their control littermates exposed to cold stress (4 °C) or housed at room temperature (24 °C). c Representative H&E stain of BAT and iWAT of wild-type and STING^gt mice. Scale bar: 200 µM. Immunoblot analysis of UCP1 expression and the phosphorylation of PKA substrates, HSL, TBK1, and IRF3 in primary-cultured inguinal adipocytes treated with 1 μM CL316243 in the presence or absence of 10 nM 2′3′-cGAMP from d STING^gt or e cGAS^−/− mice and their wild-type control mice. Glycerol release from primary-cultured inguinal adipocytes treated with 1 μM CL316243 in the presence or absence of 10 nM 2′3′-cGAMP from f STING^gt or g cGAS^−/− mice and their wild-type control mice (n = 3 for each group). h Immunoblot analysis of UCP1 expression and the phosphorylation of PKA substrates, HSL, TBK1, and IRF3 in cGAS or STING overexpressed primary inguinal adipocytes treated with 1 μM CL316243 for 12 h. i A graphic model on the negative regulation of thermogenesis by the cGAS–STING pathway in adipose tissue. Data are presented as mean ± SEM of biologically independent samples, *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed t-test (for comparison between two groups) or one-way ANOVA (for comparison of multiple groups).