Mechanism for obesity-induced increase in myocardial lipid peroxidation

OBJECTIVE: To determine the mechanisms underlying the obesity-induced increase in myocardial lipid peroxidation in the fa/fa rat. We hypothesized that elevated heart work (ie rate-pressure product), an increased rate of superoxide (oxygen free radical) production, total myocardial lipid content, and/or insufficient antioxidant defenses are potential contributors to myocardial lipid peroxidation in obesity. DESIGN: Comparative, experimental study of myocardial tissue in 16-week-old lean control (Fa/?, normal diet), obese high-fat fed (Fa/?, 45% dietary fat), and obese fatty (fa/fa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work (heart rate x systolic blood pressure), myocardial lipid content, oxidative and antioxidant enzyme activities (citrate synthase (CS), catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD)), the rate of papillary muscle superoxide radical production in vitro, thiol content, basal and post-oxidative challenge myocardial lipid peroxidation levels using thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides (PEROX) as indices of lipid peroxidation. RESULTS: Compared to lean controls, the high-fat fed and fatty animals had similar elevations (P < 0.05) in myocardial TBARS and PEROX (23%, 25% and 29% 45%, respectively; P < 0.05), and elevated susceptibilities to oxidative stress in vitro following exposure to oxidizing agents (P < 0.05). Resting heart work was slightly higher (P < 0.05) in both the high-fat fed and fatty animals compared to controls. Myocardial lipid content, SOD activities and non-protein thiol (glutathione) levels were elevated (P < 0.05) in high-fat fed and fatty animals compared to controls. The rate of superoxide formation by isolated papillary muscles in vitro did not differ among groups (P < 0.05). Regression analysis revealed that the myocardial lipid content contributed most to myocardial lipid peroxidation (R2=0.76, P < 0.05). CONCLUSIONS: Myocardial oxidative injury is closely associated with myocardial lipid content, but is not closely correlated with heart work, insufficient antioxidant defenses or a greater rate of superoxide production.