Excess oxidative stress in genetically obese rats is independent of elevated inflammatory markers (693.11)

Abstract

Oxidative stress is elevated in obese humans and rodents and may contribute to obesity‐associated conditions. These conditions include elevated blood pressure, lipids, glucose, and insulin resistance, all of which are components of the metabolic syndrome and are present in the spontaneously hypertensive obese (SHROB/Kol) rat model of prediabetes. In the present study, SHROB (N=27) were compared to lean SHR/Kol (N=11) littermates obtained from Charles River Labs (Wilmington,MA). Oxidative stress was measured by assay of peroxides by the ferric orange xylenol method (Sigma, St. Louis, MO) and nitrotyrosine by immunoassay. Plasma and organ lipid peroxides were increased up to 3‐fold in SHROB rats relative to lean SHR. Nitrotyrosine immunoreactivity in solublized kidney extracts was increased by genetic obesity (SHROB: 290±52 vs SHR: 4.1±1.3 pmol/g wet weight). Similar results were obtained for liver. The activity in the liver cytosol of the protective enzyme superoxide dismutase was not different (SHROB: 63±5 vs SHR: 53±7 U/mg protein). Another protective enzyme, catalase, was also unchanged in the liver cytosol (SHROB: 95±6 vs SHR: 93±13 U/mg protein). Thus, the enzymes responsible for breaking down reactive oxygen species fail to up‐regulate in response to increased oxidative stress in SHROB. We tested whether increased oxidative stress may reflect inflammation in SHROB rats. The inflammatory markers tumor necrosis factor alpha (TNF‐a) and interleukin‐6 in plasma did not differ between SHROB and SHR (P>0.3 for each). The anti‐inflammatory mediator adiponectin was actually increased in plasma from SHROB (N = 15) relative to SHR (N = 11; 12.2 ± 0.3 versus 9.27 ± 0.6 ug/ml). Thus the increased oxidative stress in genetically obese and hypertensive SHROB rats is not a consequence of a global inflammatory state.Grant Funding Source: Supported by Ophthalmology Education Worldwide