Author's personal copy Regular moderate exercise reduces advanced glycation and ameliorates early diabetic nephropathy in obese Zucker rats Peter Boor a,b,c, ⁎ , Peter Celec d , Michal Behuliak d , Peter Grančič e , Anton Kebis e , Marián Kukan e , Nadežda Pronayová f , Tibor Liptaj f , Tammo Ostendorf b , Katarína Šebeková a a Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, 833 03 Bratislava, Slovakia b Division of Nephrology, RWTH University of Aachen, 52074 Aachen, Germany c Institute of Pathology, RWTH University of Aachen, 52074 Aachen, Germany d Institute of Pathophysiology and Department of Molecular Biology, Comenius University, 81372 Bratislava, Slovakia e Slovak Centre for Organ Transplantation, Slovak Medical University, 83303 Bratislava, Slovakia f Institute of Analytical Chemistry, Slovak Technical University, 81237 Bratislava, Slovakia Received 3 May 2009; accepted 29 May 2009 Abstract Advanced glycation end products (AGEs) play a key role in the pathogenesis of diabetes and its complications, including the diabetic nephropathy. The renoprotective effects of exercise are well known; however, the mechanisms remain elusive. Here we examined whether a regular moderate exercise in obese Zucker rats (OZR), a model of diabetes- and obesity-associated nephropathy, will affect the development of early renal injury in OZR possibly via alteration of AGEs formation. The OZR were left without exercise (sedentary) or subjected to 10 weeks intermittent treadmill running of moderate intensity. Compared with sedentary OZR, kidneys of running OZR had significantly less glomerular mesangial expansion and tubulointerstitial fibrosis. Running OZR had significantly lower plasma AGEs-associated fluorescence and N ɛ -carboxymethyllysine. Correspondingly, renal AGEs and N ɛ -carboxymethyllysine content were lower in running OZR. Systemically, exercise increased aerobic metabolism, as apparent from urinary metabolite profiling. No differences in plasma glucose, insulin, or lipid profile were found between the 2 groups. Apart from lower advanced oxidation protein products (a marker of myeloperoxidase activity), no other marker of inflammation was altered by exercise, either systemically or locally in kidneys. No indication of changed oxidative status was revealed between the groups. Exercise in OZR decreased advanced glycation. This might represent the early event of exercise-induced renoprotection in diabetic nephropathy in OZR. If confirmed in clinical studies, regular moderate exercise could represent an easy and effective nonpharmacologic approach to reduce advanced glycation. © 2009 Elsevier Inc. All rights reserved. 1. Introduction Advanced glycation end products (AGEs) are a hetero- geneous group of compounds that accumulate in and contribute to the pathogenesis of a number of diseases including diabetes and its complications [1]. Advanced glycation end products are formed by nonenzymatic glycation, a reaction between sugars (eg, glucose or intermediates of glucose metabolism) and amino groups (eg, of peptides and proteins). Advanced glycation end products also arise during oxidative stress or inflammation. Because the main organ of AGEs disposal is the kidney, it is also one of the main targets of their deleterious effects. It is well established that AGEs induce pathologic changes in glomeruli of healthy or diabetic animals including mesangial expansion, fibrosis, and inflammation [1-6]. The effect of exercise on AGEs formation is unknown. Prevalence of end-stage renal disease due to type 2 diabetes mellitus and obesity is increasing worldwide. Effective interventions preventing the development or halting the progression of renal disease are needed [7,8]. Regular moderate aerobic exercise was shown to normalize Available online at www.sciencedirect.com Metabolism Clinical and Experimental 58 (2009) 1669 – 1677 www.metabolismjournal.com ⁎ Corresponding author. Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, 833 03 Bratislava, Slovakia. Tel.: +421 2 59370 876; fax: +421 2 59370 170. E-mail address: boor@email.cz (P. Boor). 0026-0495/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2009.05.025