The innate immune adaptor protein STING modulates lipid metabolism in an AMPK-dependent manner in Tribolium castaneum.

Stimulator of interferon genes (STING) not only plays an important role in innate immunity, but also acts as a regulator of lipid metabolism in insects. AMP-activated protein kinase (AMPK) serves as a crucial cellular energy sensor that regulates lipid homeostasis. However, the interplay between STING and AMPK remains largely unknown in insects. In this study, STING was cloned from Tribolium castaneum. Spatial-temporal expression analysis revealed that TcSTING was highly expressed in the fat body and in 7-day-old adult females, respectively. Knockdown of TcSTING significantly reduced TAG levels, decreased neutral-lipid storage in fat body lipid droplets, and lowered FAS activity concomitantly with the downregulation of genes encoding sterol regulatory element binding protein (SREBP) and fatty acid synthase (FAS1-5) in 15-day-old larvae and 2-day-old females. Conversely, knockdown of TcAMPK in 2-day-old females significantly increased the levels of TAG and neutral-lipid storage in fat body as well as FAS activity accompanied by the upregulation of TcSREBP and FAS1-5. Mechanistically, knockdown of TcSTING activated AMPK by inactivating TBK1, leading to the upregulation of phosphorylation level of acetyl-CoA carboxylase (ACC) and inhibition of the transcription of TcSREBP, whereas dsTcAMPK treatment suppressed ACC phosphorylation and activated the transcription of TcSREBP. These results demonstrate that TcSTING modulates lipid metabolism via phosphorylation regulation of AMPK, thereby altering the TAG storage.