Mechanism for obesity-induced increase in myocardial lipid peroxidation

OBJECTIVE: To determine the mechanisms underlying the obesity-induced incre ase in myocardial lipid peroxidation in the fa/fa rat. We hypothesized that elevated heart work (ie rate-pressure product), an increased rate of super oxide (O-2(.-)) production, total myocardial lipid content, and/or insuffic ient antioxidant defenses are potential contributors to myocardial lipid pe roxidation 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 fa t), and obese fatty (fa/fa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work (heart rate x systolic blood pressure), myoca rdial lipid content, oxidative and antioxidant enzyme activities (citrate s ynthase (CS), catalase (CAT), glutathione peroxidase (GPX), superoxide dism utase (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) a nd 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 2 9% 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 fat ty animals compared to controls. Myocardial lipid content, SOD activities a nd non-protein thiol (glutathione) levels were elevated (P < 0.05) in high- fat fed and fatty animals compared to controls. The rate of superoxide form ation by isolated papillary muscles in vitro did not differ among groups (P < 0.05). Regression analysis revealed that the myocardial lipid content co ntributed most to myocardial lipid peroxidation (R-2 = 0.76, P < 0.05). CONCLUSIONS: Myocardial oxidative injury is closely associated with myocard ial lipid content, but is not closely correlated with heart work, insuffici ent antioxidant defenses or a greater rate of superoxide production.