| First Author | Vila IK | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 1 | Pages | 125-139.e8 |
| PubMed ID | 34986331 | Mgi Jnum | J:321753 |
| Mgi Id | MGI:6870559 | Doi | 10.1016/j.cmet.2021.12.007 |
| Citation | Vila IK, et al. (2022) STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses. Cell Metab 34(1):125-139.e8 |
| abstractText | Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the STING (stimulator of interferon genes) protein regulates metabolic homeostasis through inhibition of the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in polyunsaturated fatty acid (PUFA) desaturation. STING ablation and agonist-mediated degradation increased FADS2-associated desaturase activity and led to accumulation of PUFA derivatives that drive thermogenesis. STING agonists directly activated FADS2-dependent desaturation, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolving STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING-targeting therapies. |
