About this Medicine article

Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome by 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 is a Medicine article available to read on EtoBox.

Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) has reached epidemic proportions with no pharmacological therapy approved. Lower circulating glycine is consistently reported in patients with NAFLD, but the causes for reduced glycine, its role as a causative factor, and its therapeutic potential remain unclear. We performed transcriptomics in livers from humans and mice with NAFLD and found suppression of glycine biosynthetic genes, primarily alanine-glyoxylate aminotransferase 1 (). Genetic ( mice) and dietary approaches to limit glycine availability resulted in exacerbated diet-induced hyperlipidemia and steatohepatitis, with suppressed mitochondrial/peroxisomal fatty acid β-oxidation (FAO) and enhanced inflammation as the underlying pathways. We explored glycine-based compounds with dual lipid/glucose-lowering properties as potential therapies for NAFLD and identified a tripeptide (Gly-Gly-L-Leu, DT-109) that improved body composition and lowered circulating glucose, lipids, transaminases, proinflammatory cytokines, and steatohepatitis in mice with established NASH induced by a high-fat, cholesterol, and fructose diet. We applied metagenomic

Author

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

Publisher

American Association for the Advancement of Science; American Association for the Advancement of Science (AAAS); Publons (ISSN 1946-6234)

Published

2020

Language

EN

Field

Medicine (Life Sciences)