| Autor: |
Alia Ghrayeb, Bella Agranovich, Daniel Peled, Alexandra C. Finney, Ifat Abramovich, Jonatan Fernandez Garcia, James Traylor, Shani Drucker, Sara Isabelle Fernandes, Natan Weissman, Y. Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
bioRxiv |
| Popis: |
SummaryNon-alcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Understanding metabolic pathways involved can provide insights into disease progression. Untargeted metabolomics of livers from mice with early-stage steatosis indicated a decrease in methylated metabolites suggesting altered one carbon metabolism. The levels of glycine, a central component of one carbon metabolism, were lower in steatotic mice, in line with clinical evidence. Isotope tracing studies demonstrated that increased synthesis of serine from glycine is the underlying cause for glycine limitation in fatty livers. Consequently, the low glycine availability in steatotic livers impaired glutathione (GSH) synthesis under oxidative stress induced by acetaminophen (APAP), enhancing hepatic toxicity. Glycine supplementation mitigated acute liver damage and overall toxicity caused by APAP in fatty livers by supportingde novoGSH synthesis. Thus, early metabolic changes in NAFLD that lead to glycine depletion sensitize mice to xenobiotic toxicity even at a reversible stage of NAFLD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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