{"title":"Both subcutaneous semaglutide and calorie restriction improves pancreatic cell hyperplasia and gut microbiota in high-fat diet-induced obese mice.","authors":"Yunfei Luo, Shiqi Yang, Haixia Zeng, Shuang Liu, Yuying Zhang, Jin-E Li, Jianping Liu","doi":"10.1186/s12986-025-00987-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obesity has emerged as a global health crisis, with its prevalence having increased alarmingly over recent decades. There is significant damage to pancreatic islets due to obesity, as well as metabolic syndrome. Improving the function of β-cells in obese patients is meaningful for treatment. Thus, GLP-1 receptor agonists like semaglutide may be beneficial for islet structural remodeling and their endocrine function in diet-induced obese mice and associated with food intake. However, whether the specific impact of semaglutide on obesity is the same as calorie restriction(CR) has not been investigated.</p><p><strong>Methods: </strong>In this study, Five-week-old male C57BL/6 mice were divided into two dietary groups and fed for 12 weeks a control diet or a high-fat diet (HFD). Then, for an additional four weeks, the main groups were resampled to include treatment (Semaglutide, SME, 40 µg/kg), or CR, totaling four groups: Control, Model, Model + SME, Model + CR. Immunofluorescence, Western blot, and RT-qPCR were used in the study.</p><p><strong>Results: </strong>Semaglutide or CR was capable of ameliorating hyperglycemia and insulin sensitivity, and reduces the lesion on the islet, increases islet cell proliferation, and recovers islet size and alpha- and beta-cell masses. Moreover, the changes include improvement of METTL3/14, pancreatic duodenal homeobox 1 (PDX-1), and insulin signaling. Meanwhile, Semaglutide or CR significantly decreases the abundance of Firmicutes, Proteobacteria, and Verrucomicrobia, but increases the Bacteroides content.</p><p><strong>Conclusions: </strong>Semaglutide plays a positive role in alleviating β-cell dysfunction by regulating gut microbiota, and METTL3/14, PDX-1, insulin signal pathway-related genes may be associated with CR.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"22 1","pages":"95"},"PeriodicalIF":4.1000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330110/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12986-025-00987-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Obesity has emerged as a global health crisis, with its prevalence having increased alarmingly over recent decades. There is significant damage to pancreatic islets due to obesity, as well as metabolic syndrome. Improving the function of β-cells in obese patients is meaningful for treatment. Thus, GLP-1 receptor agonists like semaglutide may be beneficial for islet structural remodeling and their endocrine function in diet-induced obese mice and associated with food intake. However, whether the specific impact of semaglutide on obesity is the same as calorie restriction(CR) has not been investigated.
Methods: In this study, Five-week-old male C57BL/6 mice were divided into two dietary groups and fed for 12 weeks a control diet or a high-fat diet (HFD). Then, for an additional four weeks, the main groups were resampled to include treatment (Semaglutide, SME, 40 µg/kg), or CR, totaling four groups: Control, Model, Model + SME, Model + CR. Immunofluorescence, Western blot, and RT-qPCR were used in the study.
Results: Semaglutide or CR was capable of ameliorating hyperglycemia and insulin sensitivity, and reduces the lesion on the islet, increases islet cell proliferation, and recovers islet size and alpha- and beta-cell masses. Moreover, the changes include improvement of METTL3/14, pancreatic duodenal homeobox 1 (PDX-1), and insulin signaling. Meanwhile, Semaglutide or CR significantly decreases the abundance of Firmicutes, Proteobacteria, and Verrucomicrobia, but increases the Bacteroides content.
Conclusions: Semaglutide plays a positive role in alleviating β-cell dysfunction by regulating gut microbiota, and METTL3/14, PDX-1, insulin signal pathway-related genes may be associated with CR.
期刊介绍:
Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects.
The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases.
Key areas we wish to encourage submissions from include:
-how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes;
-the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components;
-how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved;
-how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.