Effect of High‑Fat-Diet and Semaglutide on Bladder Cancer in Mice

Abstract Objective The aim of this study is to examine the proteomics of adipose tissue in mice with obesity induced by a high-fat diet, in order to investigate how obesity affects the protein expression profile of adipose tissue. Additionally, we seek to establish a foundation for understanding the mechanism through which semaglutide may impact bladder cancer (BLCA) associated with obesity.Methods Thirty-six male C57BL/6J mice, all in good health, were chosen and divided into three groups: a group fed a normal diet (referred to as the NCD group), a group fed a high-fat diet (known as the HFD group), and a group fed a high-fat diet along with semaglutide treatment (referred to as the Sema group). We examined how obesity affects serum markers and how semaglutide influences these markers. Additionally, we investigated changes in protein expression within BLCA using proteomics techniques. By employing bioinformatics methods, we identified differentially expressed proteins that may be associated with the hypothesized mechanism of semaglutide's potential for reducing bladder cancer risk.Results Our findings indicate that semaglutide has the potential to decrease body weight, enhance glucose metabolism, and improve blood lipid levels. The alterations observed in the expression of Lama2 ( laminin subunit alpha-2), Lama4 (laminin subunit alpha 4), Lamc1 (laminin subunit gamma 1), Thbs2 (thrombospondin 2) genes across the normal group, high fat group, and semaglutide group primarily involve the extracellular matrix (ECM) pathway. Following intervention with semaglutide, a significant reduction in the expression of various proteins was observed in BLCA. These results suggest that by modulating genes such as Lama2, Lama4, Lamc1, Thbs2 and others, semaglutide may potentially mitigate the risk associated with BLCA.Conclusion Semaglutide exhibits potential in mitigating obesity induced by a high-fat diet and delaying the onset and progression of bladder cancer. The activation of Lama2, Lama4, Lamc1, Thbs2, and their involvement in the ECM pathway may underlie the mechanism through which semaglutide exerts its effects on bladder cancer.