Both subcutaneous semaglutide and calorie restriction improves pancreatic cell hyperplasia and gut microbiota in high-fat diet-induced obese mice.

IF 4.1 2区 医学 Q2 NUTRITION & DIETETICS
Yunfei Luo, Shiqi Yang, Haixia Zeng, Shuang Liu, Yuying Zhang, Jin-E Li, Jianping Liu
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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.

皮下半马鲁肽和热量限制均可改善高脂肪饮食诱导的肥胖小鼠的胰腺细胞增生和肠道微生物群。
背景:肥胖已成为一种全球性的健康危机,近几十年来,其患病率惊人地增加。肥胖和代谢综合征会对胰岛造成严重损害。改善肥胖患者β-细胞功能对治疗有重要意义。因此,像semaglutide这样的GLP-1受体激动剂可能有利于饮食诱导的肥胖小鼠的胰岛结构重塑及其内分泌功能,并与食物摄入有关。然而,西马鲁肽对肥胖的具体影响是否与卡路里限制(CR)相同,尚无研究。方法:将5周龄雄性C57BL/6小鼠分为两组,分别饲喂对照组和高脂饲料(HFD) 12周。然后,在另外四周,对主要组进行重新采样,包括治疗组(Semaglutide, SME, 40µg/kg)或CR,共四组:对照组,模型组,模型+ SME组,模型+ CR组。采用免疫荧光、Western blot、RT-qPCR等方法进行研究。结果:Semaglutide或CR能够改善高血糖和胰岛素敏感性,减少胰岛病变,增加胰岛细胞增殖,恢复胰岛大小和α和β细胞团块。此外,这些变化还包括METTL3/14、胰十二指肠同源盒1 (PDX-1)和胰岛素信号的改善。同时,Semaglutide或CR显著降低了厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)和Verrucomicrobia的丰度,但增加了拟杆菌门(Bacteroides)的含量。结论:Semaglutide通过调节肠道菌群,对缓解β细胞功能障碍具有积极作用,METTL3/14、PDX-1、胰岛素信号通路相关基因可能与CR相关。
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来源期刊
Nutrition & Metabolism
Nutrition & Metabolism 医学-营养学
CiteScore
8.40
自引率
0.00%
发文量
78
审稿时长
4-8 weeks
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.
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