Protective Effect of Semaglutide on Obesity-Induced Renal Disease and Obesity-Induced Kidney Renal Clear Cell Carcinoma.

IF 2.8 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI:10.2147/DMSO.S498447

Shuqi Wang, Mengmeng Zhang, Xiaoman Yang, Shuchun Chen

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Abstract

Purpose: Proteomics was used to study the effect of semaglutide on the expression of renal protein in obese mice, and looking for proteins that could improve the prognosis of Kidney Renal Clear Cell Carcinoma (KIRC).

Materials and methods: Thirty-six mice were randomly divided into normal-fat diet group (NFD), high-fat diet group (HFD), high-fat diet plus semaglutide intervention group (HS). Collected mice serum, urine, kidney tissue samples, and detected urinary protein/creatinine, blood glucose, blood lipid, inflammation, oxidative stress and other related indicators. Different staining methods were used to analyze the pathological changes of mice's kidneys. Liquid chromatography-tandem mass spectrometry mass spectrometry (LC-MS/MS) analysis was used to analyze the total protein in the kidneys of mice. Finally, bioinformatics technology was used to analyze significantly different expressed proteins (DEPs).

Results: The mechanism of semaglutide protecting the kidneys were related to oxidative phosphorylation, PPAR signaling pathway, thiamine, butyric acid and tryptophan metabolism pathways. Moreover, semaglutide could significantly increase the expression of Man1a1 and Ntn4 in the kidneys of mice, while the high-expression of Man1a1 and Ntn4 in KIRC population had a better overall survival rate.

Conclusion: Semaglutide could regulate the development of KIRC by up-adjusting the expression of Man1a1 and Ntn4.

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西马鲁肽对肥胖肾病和肥胖肾透明细胞癌的保护作用。

目的：采用蛋白质组学方法研究西马鲁肽对肥胖小鼠肾蛋白表达的影响，寻找改善肾透明细胞癌（KIRC）预后的蛋白。材料与方法：将36只小鼠随机分为正常脂肪饮食组（NFD）、高脂肪饮食组（HFD）、高脂肪饮食加西马鲁肽干预组（HS）。采集小鼠血清、尿液、肾脏组织标本，检测尿蛋白/肌酐、血糖、血脂、炎症、氧化应激等相关指标。采用不同的染色方法分析小鼠肾脏的病理变化。采用液相色谱-串联质谱法（LC-MS/MS）对小鼠肾脏总蛋白进行分析。最后，利用生物信息学技术分析显著差异表达蛋白（DEPs）。结果：西马鲁肽保护肾脏的机制与氧化磷酸化、PPAR信号通路、硫胺素、丁酸和色氨酸代谢途径有关。此外，semaglutide可以显著增加小鼠肾脏中Man1a1和Ntn4的表达，而KIRC人群中Man1a1和Ntn4的高表达具有更好的总生存率。结论：Semaglutide可通过上调Man1a1和Ntn4的表达来调节KIRC的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

5.90

自引率

6.10%

发文量

431

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.