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• W3186372382 abstract "SUMMARY Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation in vivo is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended Trans-omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify changes in metabolic flux, and to quantify contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting ob / ob mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in liver. Highlights We created OMELET to infer metabolic flux and its regulation from multi-omic data. Gluconeogenic and pyruvate cycle fluxes increased in fasting ob / ob mice. Transcripts increases mediated the increase in gluconeogenic fluxes in ob / ob mice. Increases in transcripts and substrates enhanced pyruvate cycle flux in ob / ob mice." @default.
• W3186372382 created "2021-08-02" @default.
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• W3186372382 date "2021-06-22" @default.
• W3186372382 modified "2023-10-18" @default.
• W3186372382 title "Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism" @default.
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• W3186372382 doi "https://doi.org/10.1101/2021.06.21.449220" @default.
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