CDA HFD mice analysed for hepatic gene expression after treatment with semaglutide
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ABSTRACT:
PROVIDER: PRJNA1250966 | ENA |
REPOSITORIES: ENA
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2025-04-25 | GSE294630 | GEO
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2022-08-19 | GSE207856 | 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.
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Project description:DIO-MASH mice analysed for hepatic gene expression after treatment with semaglutide
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Project description:CDA-HFD induced NASH liver fibrosis
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2024-03-12 | GSE174542 | 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.
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2024-03-12 | GSE174543 | GEO
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.
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