Effects of obesity on development of oxidative stress and DNA damages in liver of the obese Zucker rat (643.1)

Abstract

The obesity epidemic is continuing in the United States for two decades. Obesity leads to significant change in redox balance, targeting both systemic and targeted organs/tissues. Previously, we reported obesity promotes DMBA‐induced mammary tumor development using the obese Zucker rat model. This study’s objective was to investigate the effects of obesity on oxidative stress development and oxidative DNA damage in the rat liver. Female lean and obese Zucker rats (n=8/group) at 5 weeks of age were fed AIN‐93‐G diet for 8 weeks. Liver sample metabolites were measured using HPLC‐electrochemical detection or LC‐MS. We found lean rats have significantly (P<0.05) higher levels of reduced free Glutathione (GSH), significantly (P<0.04) lower levels of oxidized Glutathione (GSSG) and 20% lower (P<0.03) GSH/GSSG oxidative ratio compared to the obese group. Also, an indicator of oxidative DNA damage, 8‐hydroxy‐Guanosine (8‐OH‐G), was 25% (P<0.03) higher in obese rats compared to the lean group and there was a significant (P<0.03) spike in 5‐hydroxymethyl‐Cytosine (5‐hmC) in obese rats. In summary, our results shows higher levels of oxidative stress in the liver of obese rats, which corresponds to an increase in DNA damage, compared to lean rats. An increase in the formation of 5‐hmC in obese rats indicates that it can be a very reliable new marker of DNA damage in addition to 8‐OH‐G.Grant Funding Source: UAMS Children’s University Medical Group