| Goliath induces inflammation in obese mice by linking fatty acid β-oxidation to glycolysis |
| 論文作者 |
Hao, SM; Zhang, SL; Ye, JL; Chen, LF; Wang, Y; Pei, SY; Zhu, QC; Xu, J; Tao, YZ; Zhou, N; Yin, HY; Duan, CW; Mao, CM; Zheng, MY; Xiao, YC |
| 期刊/會(huì)議名稱 |
EMBO REPORTS |
| 論文年度 |
2023 |
| 論文類別 |
Article |
| 摘要 |
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. |
| 期 |
4 |
| 卷 |
24 |
| 影響因子 |
7.7 |
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