Figure 5.

STING agonists promote FADS2-dependent desaturation

(A) WCEs from WT, Sting^−/−, or cGas^−/− MEFs stimulated or not with DMXAA for 2 h were analyzed by WB using indicated antibodies.

(B) Sum of omega-6 and omega-3 PUFAs, LC-PUFAs, and derivatives measured in MEFs stimulated or not with DMXAA for 6 h.

(C) WCEs from WT, Sting^−/−, or cGas^−/− MEFs stimulated or not with dsDNA for 6 and 24 h were analyzed by WB using indicated antibodies.

(D) Molecular docking of cGAMP, DMXAA, and 6 PUFAs to STING (top) or FADS2 (bottom). Color coding for ligand: LA in blue, ALA in green, AA in orange, DHA in turquoise, DGLA in brown, and EPA in magenta.

(E) Binding of Flag-purified F-Fads2 or F/HA-Sting to cGAMP was analyzed by WB using anti-Sting or anti-Fads2 antibodies.

(F) Prdm16 and Ucp1 mRNA levels in MEFs stimulated or not with DMXAA for 3 h in presence or not of the sc26196 Fads2 inhibitor (n = 3).

(G) Ucp1 mRNA levels in the VAT of Sting^−/− mice treated or not with DMXAA for 4 weeks (n = 5).

(H) Ucp1 protein levels in the VAT of Sting^−/− mice treated or not with DMXAA for 4 weeks. Representative WB, n = 3.

(I) Sting agonist promotes Fads2-dependent desaturation of PUFAs, leading to increased LC-PUFAs and derivatives, thereby driving the activation of thermogenic program genes and thermogenesis in vitro and in vivo.

All graphs present means ± SEM. p values were determined by Student’s t test. ^∗∗p < 0.01, ^∗∗∗p < 0.001.

Related to Figure S5.