In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

Toshiya Kokaji, Miki Eto, Atsushi Hatano, Katsuyuki Yugi, Keigo Morita, Satoshi Ohno, Masashi Fujii, Ken ichi Hironaka, Yuki Ito, Riku Egami, Saori Uematsu, Akira Terakawa, Yifei Pan, Hideki Maehara, Dongzi Li, Yunfan Bai, Takaho Tsuchiya, Haruka Ozaki, Hiroshi Inoue, Hiroyuki KubotaYutaka Suzuki, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda

研究成果: Article査読

抄録

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 leptin-deficient 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.

本文言語English
論文番号13719
ジャーナルScientific reports
12
1
DOI
出版ステータスPublished - 2022 12月

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