2. Academic Validation
  3. GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway

GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway

  • Biochim Biophys Acta Mol Cell Res. 2022 Sep;1869(9):119300. doi: 10.1016/j.bbamcr.2022.119300.
Luting Wu 1,  Min Zhou 1,  Tianyou Li 1,  Niu Dong 1,  Long Yi 1,  Qianyong Zhang 2,  Mantian Mi 3
Affiliations

Affiliations

  • 1 Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing 400038, People's Republic of China.
  • 2 Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing 400038, People's Republic of China. Electronic address: 248141998@qq.com.
  • 3 Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing 400038, People's Republic of China. Electronic address: mi_mantian@sina.com.
PMID: 35636559 DOI: 10.1016/j.bbamcr.2022.119300
Abstract

Exercise-induced physical endurance enhancement and skeletal muscle remodeling can prevent and delay the development of multiple diseases, especially metabolic syndrome. Herein, the study explored the association between glucagon-like peptide-1 (GLP-1) secretion and exercise, and its effect on skeletal muscle remodeling to enhance endurance capacity. We found both acute exercise and short-term endurance training significantly increased the secretion of GLP-1 in mice. Recombinant adeno-associated virus (AAV) encoding Gcg (proglucagon) was used to induce the overexpression of GLP-1 in skeletal muscle of mice. Overexpression of GLP-1 in skeletal muscle enhanced endurance capacity. Meanwhile, glycogen synthesis, glucose uptake, type I fibers proportion, and mitochondrial biogenesis were augmented in GLP-1-AAV skeletal muscle. Furthermore, the in vitro experiment showed that exendin-4 (a GLP-1 Receptor agonist) treatment remarkably promoted glucose uptake, type I fibers formation, and mitochondrial respiration. Mechanistically, the knockdown of AMPK could reverse the effects imposed by GLP-1R activation in vitro. Taken together, these results verify that GLP-1 regulates skeletal muscle remodeling to enhance exercise endurance possibly via GLP-1R signaling-mediated phosphorylation of AMPK.

Keywords

Endurance capacity; GLP-1; Glycogen storage; Mitochondrial biogenesis; Muscle fiber type.

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