Semaglutide attenuates obesity-induced impact on intestinal epithelium
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1085697 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28273517_1.fastq.gz | Fastqsanger.gz | |||
| SRR28273517_2.fastq.gz | Fastqsanger.gz | |||
| SRR28273518_1.fastq.gz | Fastqsanger.gz | |||
| SRR28273518_2.fastq.gz | Fastqsanger.gz | |||
| SRR28273519_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Obesity, a complex ailment, has demonstrated promising weight reduction outcomes with glucagon-like peptide-1 receptor agonists (GLP-1RA) drugs like semaglutide. Nevertheless, their intricate mechanisms remain elusive. In this study, we constructed single-cell transcriptomic profiles of intestinal epithelium from individuals with normal and high BMI, revealing significant transcriptomic and metabolic alterations.
2025-03-03 | GSE261178 | GEO
Project description:Secondary hypogonadism related to male obesity (MOSH) is a common disease among male patients with severe obesity. Semaglutide has a remarkable effect in weight loss treatment. To explore the epigenetic change mechanism of Semaglutide in the treatment of MOSH, this study, through DNA methylation and miRNA sequencing, discovered the significant epigenetic changes that occurred during the treatment of MOSH with Semaglutide.
2025-07-17 | GSE302472 | GEO
Project description:Patients with heart failure with preserved ejection fraction (HFpEF) often have an unfavorable cardiometabolic profile, and obesity-related HFpEF has become a well-recognized HFpEF sub-phenotype. Targeting this unfavorable cardiometabolic profile may therefore represent a rational treatment strategy. The glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide has been shown to induce significant weight loss and to improve cardiovascular outcomes. In this study, we investigated the cardiometabolic effects of semaglutide in a representative mouse model of HFpEF and compared it to the effects of weight loss by caloric restriction.
2024-01-26 | PXD034625 | Pride
Project description:Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to impact glucose homeostasis and, more recently, the somatotropic axis. While the effects of GLP-1RAs have been extensively studied in the context of diet-induced obesity, their impact on physiology in other nutritional contexts have been less explored. We investigated the potential beneficial effects of the GLP-1RA semaglutide during juvenile protein malnutrition, a dietary challenge known to cause stunted growth and to disrupt metabolic homeostasis. We used a murine model to assess the effects of twice-weekly subcutaneous injections of semaglutide during juvenile protein malnutrition. Glucose metabolism was evaluated through in vivo oral glucose tolerance test, ex vivo glucose-stimulated insulin secretion in isolated pancreatic islets and histology of the pancreas. We combined linear growth monitoring, analysis of the growth hormone/insulin-like growth factor 1 signaling pathway and liver bulk RNA sequencing to characterize the effects of semaglutide on the somatotropic axis during juvenile protein malnutrition. Semaglutide improved glucose tolerance in control and malnourished mice, but differentially impacted pancreatic islet physiology depending on the dietary protein intake. While semaglutide did not alter growth in control conditions, it further inhibited growth of malnourished mice associated with reduction in fat but not lean mass. Surprisingly, semaglutide had no discernible effect on the functionality of the somatotropic axis in malnourished mice. Liver transcriptomics revealed that semaglutide could interfere with the growth of malnourished juvenile mice by altering circadian rhythm and thermogenesis. Our data reveal that semaglutide interacts differentially with the physiology of juvenile mice depending on their dietary protein intake. We found that semaglutide influences glucose metabolism and linear growth in a diet-dependent manner, underscoring the importance of examining the effects of GLP-1RAs across various nutritional contexts and developmental stages.
2024-05-07 | GSE266477 | GEO
Project description:Abstract. Background and aims: Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic medication that has recently been approved for treatment of obesity as well. Semaglutide is also postulated to be a promising candidate for treatment of non-alcoholic steatohepatitis (NASH). Here, we evaluated the effects of semaglutide in a translational diet-induced model with advanced NASH and fibrosis. Methods: Ldlr-/-.Leiden mice received a fast food diet (FFD) for 25 weeks, followed by another 12 weeks on FFD with daily subcutaneously injections of semaglutide or vehicle (control). Plasma parameters were evaluated, livers and hearts were examined and hepatic transcriptome analysis was performed. Results: In the liver, semaglutide significantly reduced macrovesicular steatosis (-74%, p<0.001), inflammation (-73%, p<0.001) and completely abolished microvesicular steatosis (-100%, p<0.001). Histological and biochemical assessment of hepatic fibrosis showed no significant effects of semaglutide. However, digital pathology revealed significant improvements in the degree of collagen fiber reticulation (-12%, p<0.001). Semaglutide did not affect atherosclerosis relative to controls. Additionally, we compared the transcriptome profile of FFD-fed Ldlr-/-.Leiden mice with a human gene set that differentiates human NASH patients with severe fibrosis from those with mild fibrosis. In FFD-fed Ldlr-/-.Leiden control mice, this gene set was upregulated as well, while semaglutide predominantly reversed this gene expression. Conclusions: Using a translational model with advanced NASH, we demonstrated that semaglutide is a promising candidate with particular potential for treatment of hepatic steatosis and inflammation, while for reversal of advanced fibrosis, combinations with other NASH agents may be necessary.
2023-08-01 | GSE226496 | GEO
Project description:Modulation of metabolic, inflammatory, and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. We show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation, and reduced hepatic expression of fibrosis- and inflammation-related gene pathways.
2025-04-25 | GSE294629 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. We show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation, and reduced hepatic expression of fibrosis- and inflammation-related gene pathways.
2025-04-25 | GSE294630 | GEO
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. We measured gene expression in colon epithelium from wild type mice and NAG-1 (non-steroidal anti-inflammatory drug (NSAID)-activated gene-1) transgenic mice fed either a 10% fat diet (LF) or a 60% fat diet (HF) for 20 weeks, using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol. The ChIP-seq component of the study is included in GSE46748.
2014-01-13 | E-GEOD-46843 | biostudies-arrayexpress
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. ChIP sequencing of active enhancer mark h3k27ac in colon epithelium from wild type mice and NAG-1 transgenic mice treated with either low-fat diet or high-fat diet. The gene expression component of the study is included in GSE46843.
2014-01-16 | E-GEOD-46748 | biostudies-arrayexpress
Project description:Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.
2024-03-26 | GSE262105 | GEO