An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism

Oct 28, 2022Drug design, development and therapy

Semaglutide improves muscle loss and fat gain in obese mice by changing muscle metabolism

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Semaglutide treatment resulted in a significant reduction in body weight and an increase in gastrocnemius weight in male C57BL/6 mice.

Food intake and body weight decreased after Semaglutide treatment.
Relative gastrocnemius weight ratio increased significantly following treatment.
Levels of triglycerides, cholesterol, LDL, HDL, and inflammatory markers decreased remarkably.
Histological analysis indicated improved muscle structure, with increased muscle fiber density and length.
A total of 141 differential metabolites were identified, primarily involving lipids and organic acids.
Metabolic changes were enriched in 9 pathways related to various amino acids.

AI simplified

PURPOSE: 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.

Key numbers

29.67%

Body Weight Reduction

Weight difference between HFD+S group and HFD group by study end.

141

Differential Metabolites Identified

Number of metabolites affected in gastrocnemius tissue after Semaglutide intervention.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗

An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Key numbers

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief