Proteomic Analyses of Cysteine Redox in High-fat-fed and Fasted Mouse Livers: Implications for Liver Metabolic Homeostasis

Intensive oxidative stress occurs during high-fat-diet-induced hepatic fat deposition, suggesting a critical role for redox signaling in liver metabolism. Intriguingly, lines of evidence show that fasting could also result in redox profile changes, largely through reduced oxidant and/or increased anti-oxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thus hindering our understanding of liver metabolic homeostasis. In this study, we employed a proteomic approach which combines iodoTMT and nanoLC-MS/MS to quantitatively probe the effects of high-fat-feeding and fasting on in vivo redox-based cysteine modifications. Collectively, we identified 1258 redox cysteine sites in 603 proteins and quantified 846 sites in 403 proteins.