| First Author | Hao S | Year | 2023 |
| Journal | EMBO Rep | Volume | 24 |
| Issue | 4 | Pages | e56932 |
| PubMed ID | 36862324 | Mgi Jnum | J:345488 |
| Mgi Id | MGI:7579517 | Doi | 10.15252/embr.202356932 |
| Citation | Hao S, et al. (2023) Goliath induces inflammation in obese mice by linking fatty acid beta-oxidation to glycolysis. EMBO Rep 24(4):e56932 |
| abstractText | Obesity is associated with metabolic disorders and chronic inflammation. However, the obesity-associated metabolic contribution to inflammatory induction remains elusive. Here, we show that, compared with lean mice, CD4(+) T cells from obese mice exhibit elevated basal levels of fatty acid beta-oxidation (FAO), which promote T cell glycolysis and thus hyperactivation, leading to enhanced induction of inflammation. Mechanistically, the FAO rate-limiting enzyme carnitine palmitoyltransferase 1a (Cpt1a) stabilizes the mitochondrial E3 ubiquitin ligase Goliath, which mediates deubiquitination of calcineurin and thus enhances activation of NF-AT signaling, thereby promoting glycolysis and hyperactivation of CD4(+) T cells in obesity. We also report the specific GOLIATH inhibitor DC-Gonib32, which blocks this FAO-glycolysis metabolic axis in CD4(+) T cells of obese mice and reduces the induction of inflammation. Overall, these findings establish a role of a Goliath-bridged FAO-glycolysis axis in mediating CD4(+) T cell hyperactivation and thus inflammation in obese mice. |
