Author:
Kokaji Toshiya,Eto Miki,Hatano Atsushi,Yugi Katsuyuki,Morita Keigo,Ohno Satoshi,Fujii Masashi,Hironaka Ken-ichi,Ito Yuki,Egami Riku,Uematsu Saori,Terakawa Akira,Pan Yifei,Maehara Hideki,Li Dongzi,Bai Yunfan,Tsuchiya Takaho,Ozaki Haruka,Inoue Hiroshi,Kubota Hiroyuki,Suzuki Yutaka,Hirayama Akiyoshi,Soga Tomoyoshi,Kuroda Shinya
Abstract
AbstractMetabolic 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.
Funder
Japan Society for the Promotion of Science
Japan Science and Technology Agency
Adaptable and Seamless Technology Transfer Program through Target-Driven R and D
Japan Agency for Medical Research and Development
Publisher
Springer Science and Business Media LLC