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

• Published in: Journal of proteome research 2018-01, Vol.17 (1), p.129-140
• Main Authors: Li, Yixing, Luo, Zupeng, Wu, Xilong, Zhu, Jun, Yu, Kai, Jin, Yi, Zhang, Zhiwang, Zhao, Shuhong, Zhou, Lei
• Format: Article
• Language: English
• Subjects: Animals; Cysteine - metabolism; Diet, High-Fat; Fasting - metabolism; Homeostasis; Lipid Metabolism; Liver - metabolism; Metabolic Networks and Pathways; Mice; Oxidation-Reduction; Proteomics
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.7b00431

Intensive oxidative stress occurs during high-fat-diet-induced hepatic fat deposition, suggesting a critical role for redox signaling in liver metabolism. Intriguingly, evidence shows that fasting could also result in redox-profile changes largely through reduced oxidant or increased antioxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thereby hindering our understanding of liver metabolic homeostasis. We employed a proteomic approach combining iodoacetyl tandem mass tag and nanoliquid chromatography tandem mass spectrometry to quantitatively probe the effects of high-fat feeding and fasting on in vivo redox-based cysteine modifications. Compared with control groups, ∼60% of cysteine residues exhibited downregulated oxidation ratios by fasting, whereas ∼94% of these ratios were upregulated by high-fat feeding. Importantly, in fasted livers, proteins exhibiting diminished cysteine oxidation were annotated in pathways associated with fatty acid metabolism, carbohydrate metabolism, insulin, peroxisome proliferator-activated receptors, and oxidative respiratory chain signaling, suggesting that fasting-induced redox changes targeted major metabolic pathways and consequently resulted in hepatic lipid accumulation.