Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome

著者: Oren Rom, Yuhao Liu, Zhipeng Liu, Ying Zhao, Jianfeng Wu, Alia Ghrayeb, Luis Villacorta, Yanbo Fan, Lin Chang, Lu Wang, Cai Liu, Dongshan Yang, Jun Song, Jason C. Rech, Yanhong Guo, Huilun Wang, Guizhen Zhao, Wenying Liang, Yui Koike, Haocheng Lu, Tomonari Koike, Tony Hayek, Subramaniam Pennathur, Chuanwu Xi, Bo Wen, Duxin Sun, Minerva T. Garcia-Barrio, Michael Aviram, Eyal Gottlieb, Inbal Mor, Wanqing Liu, Jifeng Zhang, Y. Eugene Chen - Science Translational Medicine 2020 被引用: 279

sensu stricto was markedly increased in mice with NASH and decreased after DT-109 treatment. DT-109 induced hepatic FAO pathways, lowered lipotoxicity, and stimulated de novo glutathione synthesis. In turn, inflammatory infiltration and hepatic fibrosis were attenuated via suppression of NF-κB target genes and TGFβ/SMAD signaling. Unlike its effects on the gut microbiome, DT-109 stimulated FAO and glutathione synthesis independent of NASH. In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation.