Semaglutide and adenosine alleviate obesity-induced kidney injury, with observed modulation of the Txnip/NLRP3 pathway.

OBJECTIVE: This study was designed to evaluate the effects of Semaglutide and adenosine on kidney protein expression in obese mice induced by a high-fat diet (HFD), to identify signaling pathways involved in the obesity-related glomerulonephropathy (ORG) regulation using a proteomics approach. MATERIALS AND METHODS: A total of 48 mice were divided into normal-fat diet (NFD), high-fat diet (HFD), HFD + semaglutide intervention (HS), and HFD + adenosine intervention (HA) groups. Mouse serum, urine, and kidney tissue samples were collected to identify markers for blood glucose lipid metabolism, inflammation, oxidative stress (OS), kidney damage protein, urinary protein/creatinine, and other relevant factors. The kidney pathological changes of mice were observed under light and electron microscope. The differences in total proteins in the kidneys of mice were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteins with significant differences were selected for bioinformatics and Western Blot (WB) analyses. RESULTS: Semaglutide and adenosine can reduce the weight of obese mice, improve the level of glucose and lipid metabolism, inflammation, and OS in obese mice, and have a positive effect on glomerular and tubular lesions in mice. The TXNIP/NLRP3 signaling pathway, which is involved in the pathogenesis of murine ORG, was screened using a proteomics approach. Western Blot showed that the expressions of Txn, Txnip, and NLRP3 in HFD mice were significantly higher than those of NFD mice, while the expression levels of Txn, Txnip, and NLRP3 in HS and HA mice were substantially lower than those of HFD mice. CONCLUSION: Semaglutide and adenosine can ameliorate obesity-induced renal injury, potentially through modulation of the Txnip/NLRP3 pathway.