ADAM17; Obesidad; Células tubulares proximales renalesADAM17; Obesity; Renal proximal tubular cellsADAM17; Obesitat; Cèl·lules tubulars proximals renalsAcute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.This research was funded by ISCIIII-FEDER grant numbers PI16/00620 and PI17/00257; ISCIII-RETICS REDinREN RD16/0009/0013, and ISCIII-RICORS RD21/0005. C.B. is also funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS STL008/18/00018 to develop clinical and epidemiological studies mainly focused on diabetes and its associations with new biomarkers. V.P. is a research fellow of ISCIII-FSE project FI17/00025
