Obesity is associated with increased myocardial oxidative stress

OBJECTIVE: To determine: 1) whether obesity predisposes the myocardium to o xidative stress as evidenced by higher tissue levels of myocardial lipid pe roxidation, and 2) what cellular mechanisms are responsible for this predis position. DESIGN: Comparative, descriptive study of the myocardial tissue of lean and obese Fatty Zucker animals. ANIMALS: 12 month old lean (-/fa; n=6; mean body weight=590 g) and obese (f a/fa; na = 7; mean body weight = 882 g) male Fatty Zucker rats. MEASUREMENTS: Basal lipid peroxidation (assessed using thiobarbituric react ive acid substances (TBARS) and cumene hydroperoxide equivalents), oxidativ e and antioxidant enzyme activities (citrate synthase (CS), superoxide dism utase (SOD), glutathione peroxidase (GPX) and catalase (CAT), thiol content , heat shock protein expression (HSP72/73) and TEARS concentrations followi ng an iron-mediated challenge in vitro. RESULTS: Compared to lean, lipid peroxidation was greater (P < 0.05) in the left ventricle (LV) from obese rats as indicated by higher levels of lipid hydroperoxides (mean = 11.48 vs 13.7 cumene hydroperoxide equivalents (CHP E)/mg lipid) and TEARS (mean = 11.1 vs 13.9 nMol/mg lipid.). The activity o f the manganese isoform of superoxide dismutase in the LV was higher (P ( 0 .05) in obese animals, compared to controls (mean = 135 vs 117 U/mg protein ). In contrast, LV catalase and glutathione peroxidase activities did not d iffer (P > 0.05) between groups. Also, LV levels of HSP 72 (inducible) and 73 (constitutive) did not differ (P > 0.05)(between lean and obese animals. Following an iron-stimulated oxidative challenge in vitro, TEARS concentra tion was significantly greater (P < 0.05) in LV of obese rats compared to t he lean (mean = 12.7 vs 16.7 nMol/mg lipid). CONCLUSIONS: These results support the notion that obesity predisposes the myocardium to oxidative stress. However, the postulate that obesity is asso ciated with elevated myocardial antioxidant enzyme activities and HSPs was only partially supported by these findings.