Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism

Saori Uematsu, Satoshi Ohno, Kaori Y. Tanaka, Atsushi Hatano, Toshiya Kokaji, Yuki Ito, Hiroyuki Kubota, Ken ichi Hironaka, Yutaka Suzuki, Masaki Matsumoto, Keiichi I. Nakayama, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 relative changes in metabolic flux, and to calculate 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 the liver.

Original languageEnglish
Article number103787
JournaliScience
Volume25
Issue number2
DOIs
Publication statusPublished - 2022 Feb 18

Keywords

  • Metabolomics;
  • Proteomics
  • Systems biology
  • Transcriptomics

ASJC Scopus subject areas

  • General

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