Impact of weight loss induced by gastric bypass or caloric restriction on oxidative stress and genomic damage in obese Zucker rats

Background: Evidence on bariatric surgery induced weight loss and its possible impact on cancer risk is limited, but also controversial. We used obese Zuckerfaifa and lean Zuckerfai-' to investigate the association between obesity, oxidative stress and genomic damage after weight loss induced either by Roux en-Y gastric bypass surgery (RYGB) or caloric restriction. Methods: Male Zuckerfaifa rats underwent RYGB (n=15) or sham surgery (n=17). Five shams were food restricted and body weight matched (BWM) to RYGB. Twelve Zuckerfai rats served as lean controls. Body weight and food intake were measured daily. An oral glucose tolerance test was performed on day 27. DHE staining and western blots of HSP70 and HO-1 were used to evaluate oxidative stress and anti-3nitrotyrosine antibody staining for nitrative stress detection in colon and kidney. Lipid peroxidation products in urine were quantified by TBARS assay. LC/MS/MS was applied to measure urinary excretion of 8-oxoGua (oxidized DNA derived base), 8-oxodG (oxidized DNA derived nucleoside) and 8-oxoGuo (oxidized RNA derived nucleoside). DNA double strand breaks (DS6s) and cell proliferation (PCNA) were detected by immunohistochemistry. Results: Sham-operated rats showed impaired glucose tolerance, elevated plasma insulin levels as well as elevated oxidative stress and nitrative stress markers, which were less severe after weight loss by RYGB or caloric restriction. Cell proliferation showed similar trends but no significant alteration. DNA DSBs were more frequent in sham-operated compared to all other groups. DNA damage in Zuckerfaifa rats positively correlated with basal plasma insulin values (Spearman's correlation coefficient for colon, 0.634 and for kidney, 0.525). Conclusions: RYGB and caloric restriction were sufficient to significantly reduce elevated oxidative/nitrative stress and genomic damage in obese Zuckerfaifa rats. Further investigations are needed to elucidate the underlying mechanism of these genome protective effects. (C) 2016 Elsevier Inc. All rights reserved.