GSE262105 Semaglutide ameliorates cardiac remodeling by optimizing energy substrate utilization and through the Creb5/NR4a1 axis in male mice

Contributors : Yu-Lan Ma ; Chun-Yan Kong ; Zhen Guo ; Qi-Zhu TangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSemaglutide (Sema) is a novel glucagon-like peptide-1 receptor (GLP-1R) agonist that is used clinically as a hypoglycemic and bariatric agent, as it regulates the energy metabolic process. In heart failure, mitochondrial oxidative phosphorylation substrates are altered, glycolysis is increased, and intracellular energy production is decreased. However, the responsiveness of Sema-regulated energy metabolism to the metabolic environment of cardiomyocytes stimulated by pressure burden remains unclear. Herein, we used transverse aortic constriction (TAC) surgery as the disease model. We found that Sema improved cardiac dysfunction and attenuated myocardial hypertrophy and fibrosis. This is manifested by reduced myocyte volume and interstitial collagen deposition. We found that Sema treatment maintains mitochondrial morphology and function under conditions of chronic stress load-mediated damage. Untargeted metabolomics analysis revealed that Sema ameliorated mitochondrial lesions and reduced lipid accumulation and ATP insufficiency by promoting glycolytic species products enter the tricarboxylic acid cycle (TCA) and increasing β-oxidation. Transcriptional profiling results revealed that Sema exerted its effects on myocardial energy metabolism by regulating Creb5/NR4a1 in the canonical PI3K/AKT pathway. Specifically, Sema reduc...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research