Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle

Riku Egami, Toshiya Kokaji, Atsushi Hatano, Katsuyuki Yugi, Miki Eto, Keigo Morita, Satoshi Ohno, Masashi Fujii, Ken ichi Hironaka, Saori Uematsu, Akira Terakawa, Yunfan Bai, Yifei Pan, Takaho Tsuchiya, Haruka Ozaki, Hiroshi Inoue, Shinsuke Uda, Hiroyuki Kubota, Yutaka Suzuki, Masaki MatsumotoKeiichi I. Nakayama, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.

Original languageEnglish
Article number102217
JournaliScience
Volume24
Issue number3
DOIs
Publication statusPublished - 2021 Mar 19

Keywords

  • Biological Sciences
  • Endocrinology
  • Metabolomics
  • Omics
  • Proteomics
  • Systems Biology
  • Transcriptomic

ASJC Scopus subject areas

  • General

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