PT  - JOURNAL ARTICLE
AU  - Toshiya Kokaji
AU  - Miki Eto
AU  - Atsushi Hatano
AU  - Katsuyuki Yugi
AU  - Keigo Morita
AU  - Satoshi Ohno
AU  - Masashi Fujii
AU  - Ken-ichi Hironaka
AU  - Yuki Ito
AU  - Riku Egami
AU  - Saori Uematsu
AU  - Akira Terakawa
AU  - Yifei Pan
AU  - Hideki Maehara
AU  - Dongzi Li
AU  - Yunfan Bai
AU  - Takaho Tsuchiya
AU  - Haruka Ozaki
AU  - Hiroshi Inoue
AU  - Hiroyuki Kubota
AU  - Yutaka Suzuki
AU  - Akiyoshi Hirayama
AU  - Tomoyoshi Soga
AU  - Shinya Kuroda
TI  - In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states
AID  - 10.1101/2022.03.27.486003
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.27.486003
4099  - http://biorxiv.org/content/early/2022/03/28/2022.03.27.486003.short
4100  - http://biorxiv.org/content/early/2022/03/28/2022.03.27.486003.full
AB  - Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and genetically obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.Competing Interest StatementThe authors have declared no competing interest.