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

Shuqi Wang,1,2 Mengmeng Zhang,1,2 Xiaoman Yang,1,2 Shuchun Chen1– 3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Key Laboratory of Metabolic Diseases in Hebei Province, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email [email protected]: 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.Keywords: obesity, semaglutide, kidney renal clear cell carcinoma, proteomics