Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2

Kaiyi Zhang; Ning Xie; Huaqiong Ye; Jiakun Miao; Boce Xia; Yu Yang; Huanqi Peng; Shuang Xu; Tianwen Wu; Cong Tao; Jinxue Ruan; Yanfang Wang; Shulin Yang

doi:10.1016/j.isci.2023.108590

Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2

iScience. 2023 Nov 29;27(1):108590. doi: 10.1016/j.isci.2023.108590. eCollection 2024 Jan 19.

Authors

Kaiyi Zhang^{1

2}, Ning Xie¹, Huaqiong Ye¹, Jiakun Miao¹, Boce Xia¹, Yu Yang¹, Huanqi Peng¹, Shuang Xu¹, Tianwen Wu¹, Cong Tao¹, Jinxue Ruan³, Yanfang Wang¹, Shulin Yang¹

Affiliations

¹ State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
² Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, 5030 Gembloux, Belgium.
³ Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China.

Abstract

Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4^m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4^m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mechanisms and identifying clinical targets for metabolic diseases.

Keywords: Comp; Genomics; Metabolomics; Omics; Proteomics.