Mouse and rat liver and liver cell line LC-MS/MS

This study sought to interrogate the effects of lipids and lipid metabolites on the hepatic proteome. Protein expression and tyrosine phosphorylation in high-fat diet (HFD) mouse livers vs. livers of normal chow fed (NC) mice were investigated using multiplexed quantitative LC-MS/MS (TMT labeling). Additionally, the rat hepatoma cell line H4IIE was used to monitor the effects of free fatty acids on tyrosine signaling, gene expression and the levels of reactive oxygen species. These data were used to inform potential points of intervention and chemical perturbations and their effects on phenotypic and signaling output in the cell line, and included small molecule inhibtors of Src-family kinases and antioxidants. Based on the in vitro effects, HFD mice were fed an antioxidant and phenotypic and tyrosine signaling changes were measured.