Personal model-assisted identification of NAD⁺ and glutathione metabolism as intervention target in NAFLD.

ABSTRACT: To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD⁺ and glutathione (GSH) in subjects with high HS Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepati

SUBMITTER: Mardinoglu A 

PROVIDER: S-EPMC5371732 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature