Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy
Kunpeng Liu, Dongbo Qiu, Xue Liang, Yingqi Huang, Yao Wang, Xin Jia, Kun Li, Jingyuan Zhao, Cong Du, Xiusheng Qiu, Jun Cui, Zhen‐Dong Xiao, Yunfei Qin, Qi Zhang
Abstract
: AA: amino acid; ACTB: actin beta; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; DEPTOR: DEP domain containing MTOR interacting protein; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FFAs: free fatty acids; GFP: green fluorescent protein; HFD: high-fat diet; HT-DNA: herring testis DNA; IL1B: interleukin 1 beta; LAMP1: lysosomal associated membrane protein 1; LDs: lipid droplets; MAP1LC3: microtubule associated protein 1 light chain 3; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MLST8: MTOR associated protein, LST8 homolog; MT-ND1: mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1; mtDNA: mitochondrial DNA; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NAFL: nonalcoholic fatty liver; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; NPCs: non-parenchymal cells; PA: palmitic acid; PLIN2: perilipin 2; RD: regular diet; RELA: RELA proto-oncogene, NF-kB subunit; RPS6: ribosomal protein S6; RPS6KB1: ribosomal protein S6 kinase B1; RPTOR: regulatory associated protein of MTOR complex 1; RRAGA: Ras related GTP binding A; RRAGC: Ras related GTP binding C; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGs: triglycerides; TREX1: three prime repair exonuclease 1.