Huang, Ji Rajapakse, Angana Xiong, Yuyan Montani, Jean-Pierre Verrey, François Ming, Xiu-Fen Yang, Zhihong 2016 Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II^−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II^−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg- II^−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II^−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development. application/pdf https://folia.unifr.ch/global/documents/305232 https://folia.unifr.ch/documents/305232/files/yan_gta.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3389/fphys.2016.00560 info:eu-repo/semantics/openAccess License undefined Frontiers in Physiology. - 2016, vol. 7, p. 560 info:eu-repo/classification/udc/57 Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity http://purl.org/coar/resource_type/c_6501