Drug Design, Development and Therapy (Oct 2022)
An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism
Abstract
Qingjuan Ren,1,2 Shuchun Chen,1,3 Xing Chen,1 Shu Niu,4 Lin Yue,5 Xiaoyu Pan,1 Zelin Li,1 Xiaoyi Chen1 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Geriatrics, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of China; 4Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 5Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-13833166283, Email [email protected]: This study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics.Methods: A total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics.Results: After Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids.Conclusion: Semaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.Keywords: sarcopenic obesity, sarcopenia, glucagon-like peptide-1 receptor agonists, Semaglutide, metabonomics
