Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity

作者：Yunfan Bai, Keigo Morita, Toshiya Kokaji, Atsushi Hatano, Satoshi Ohno, Riku Egami, Yifei Pan, Dongzi Li, Katsuyuki Yugi, Saori Uematsu, Hiroshi Inoue, Y. Inaba, Yutaka Suzuki, Masaki Matsumoto, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.109121 · 被引用次数：9 · 研究领域：Diet and metabolism studies、Liver Disease Diagnosis and Treatment、Dietary Effects on Health

Dysregulation of liver metabolism associated with obesity during feeding and fasting leads to the breakdown of metabolic homeostasis. However, the underlying mechanism remains unknown. Here, we measured multi-omics data in the liver of wild-type and leptin-deficient obese ( ob / ob ) mice at ad libitum feeding and constructed a differential regulatory trans-omic network of metabolic reactions. We compared the trans-omic network at feeding with that at 16 h fasting constructed in our previous study. Intermediate metabolites in glycolytic and nucleotide metabolism decreased in ob / ob mice at feeding but increased at fasting. Allosteric regulation reversely shifted between feeding and fasting, generally showing activation at feeding while inhibition at fasting in ob / ob mice. Transcriptional regulation was similar between feeding and fasting, generally showing inhibiting transcription factor regulations and activating enzyme protein regulations in ob / ob mice. The opposite metabolic dysregulation between feeding and fasting characterizes breakdown of metabolic homeostasis associated with obesity.