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

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Abstract
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 and/or increased antioxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thereby hindering our understanding of liver metabolic homeostasis. In this study, we employed a proteomic approach combining iodoacetyl tandem mass tag and nano-liquid 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, oxidative respiratory chain signaling, suggesting that fasting-induced redox changes targeted major metabolic pathways and consequently resulted in hepatic lipid accumulation.
Funding Information
  • Fok Ying Tong Education Foundation (141025)
  • Natural Science Foundation of Guangxi Province (2014GXNSFDA118014)
  • National Natural Science Foundation of China (31301947, 31660641)
  • Scientific Research Foundation, Guangxi University (XTZ130719)

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