title: Impact of weight loss induced by gastric bypass or caloric restriction on oxidative stress and genomic damage in obese Zucker rats.
abstract: Evidence on bariatric surgery induced weight loss and its possible impact on cancer risk is limited, but also controversial. We used obese Zucker(fa/fa) and lean Zucker(fa/+) 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.
  
  
  
  Male Zucker(fa/fa) rats underwent RYGB (n=15) or sham surgery (n=17). Five shams were food restricted and body weight matched (BWM) to RYGB. Twelve Zucker(fa/+) 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-3-nitrotyrosine 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 (DSBs) and cell proliferation (PCNA) were detected by immunohistochemistry.
  
  
  
  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 Zucker(fa/fa) rats positively correlated with basal plasma insulin values (Spearman's correlation coefficient for colon, 0.634 and for kidney, 0.525).
  
  
  
  RYGB and caloric restriction were sufficient to significantly reduce elevated oxidative/nitrative stress and genomic damage in obese Zucker(fa/fa) rats. Further investigations are needed to elucidate the underlying mechanism of these genome protective effects.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
authors.forename: Ezgi Eyluel
authors.initials: EE
authors.lastname: Bankoglu
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Seyfried
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Rotzinger
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Nordbeck
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Corteville
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jurowich
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Christoph Thomas
authors.initials: CT
authors.lastname: Germer
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Wuerzburg, Germany; Experimental Surgery, Department of General, Visceral, Vascular, and Pediatric Surgery, University Hospital of Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.affiliation: Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Str. 9, 97078 Würzburg, Germany. Electronic address: stopper@toxi.uni-wuerzburg.de.
authors.forename: Helga
authors.initials: H
authors.lastname: Stopper
mesh_terms: D000818:Animals; D050110:Bariatric Surgery / Q000009:adverse effects*; D031204:Caloric Restriction / Q000009:adverse effects*; D049109:Cell Proliferation / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D015390:Gastric Bypass / Q000009:adverse effects; D042822:Genomic Instability / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D015227:Lipid Peroxidation / Q000235:genetics; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D018384:Oxidative Stress / Q000235:genetics*; D051381:Rats; D011924:Rats, Zucker; D015431:Weight Loss / Q000235:genetics / Q000502:physiology
chemical_list: D007328:Insulin
keywords: Caloric restriction; DNA damage; Obesity; Oxidative stress; Roux-en-Y gastric bypass