%0 Journal Article
%T GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway.
%A Wu L
%A Zhou M
%A Li T
%A Dong N
%A Yi L
%A Zhang Q
%A Mi M
%A Wu L
%A Zhou M
%A Li T
%A Dong N
%A Yi L
%A Zhang Q
%A Mi M
%J Biochim Biophys Acta Mol Cell Res
%V 1869
%N 9
%D Sep 2022
%M 35636559
%F 5.011
%R 10.1016/j.bbamcr.2022.119300
%X 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.