Objective: Oxidative stress may be the unifying mechanism underlying the development of comorbidities in obesity. Evidence suggests that a clustering of sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia, increased tissue lipid levels, inadequate antioxidant defenses, increased rates of free radical formation, enzymatic sources within the endothelium, and chronic inflammation. Method: This review provides a summary of the available evidence on systemic oxidative stress in humans and specific metabolic pathways by which obesity may elevate systemic oxidant stress. The authors suggest possible methods of reducing oxidative stress such as antioxidant supplementation, caloric restriction and/or physical activity and surgical intervention to combat free radicals and reduce adipose tissue. Results: Obesity is associated with oxidative stress and can be reduced with weight loss (regardless of exercise or surgery induced weight loss), caloric restriction or antioxidant rich diets. Conclusion: Oxidative stress levels are elevated in human obesity, and these levels are modifiable with various lifestyle modifications and surgical interventions.

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.

OBJECTIVE:To determine the mechanisms underlying the obesity-induced increase in myocardial lipid peroxidation in the faafa rat. We hypothesized that elevated heart work (ie rate-pressure product), an increased rate of superoxide (O 2 À ) production, total myocardial lipid content, andaor insuf®cient antioxidant defenses are potential contributors to myocardial lipid peroxidation in obesity. DESIGN: Comparative, experimental study of myocardial tissue in 16-week-old lean control (Faa?, normal diet), obese high-fat fed (Faa?, 45% dietary fat), and obese fatty (faafa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work (heart rate  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 (R 2 0.76, P`0.05). CONCLUSIONS: Myocardial oxidative injury is closely associated with myocardial lipid content, but is not closely correlated with heart work, insuf®cient antioxidant defenses or a greater rate of superoxide production.

OBJECTIVE: To determine: 1) whether obesity predisposes the myocardium to oxidative stress as evidenced by higher tissue levels of myocardial lipid peroxidation, and 2) what cellular mechanisms are responsible for this predisposition. DESIGN: Comparative, descriptive study of the myocardial tissue of lean and obese Fatty Zucker animals. ANIMALS: 12 month old lean ( 7 afa; n 6; mean body weight 590 g) and obese (faafa; na 7; mean body weight 882 g) male Fatty Zucker rats. MEASUREMENTS: Basal lipid peroxidation (assessed using thiobarbituric reactive acid substances (TBARS) and cumene hydroperoxide equivalents), oxidative and antioxidant enzyme activities (citrate synthase (CS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT), thiol content, heat shock protein expression (HSP72a73) and TBARS concentrations following 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 (CHPE)amg lipid) and TBARS (mean 11.1 vs 13.9 nMolamg lipid.). The activity of the manganese isoform of superoxide dismutase in the LV was higher (P`0.05) in obese animals, compared to controls (mean 135 vs 117 Uamg protein). In contrast, LV catalase and glutathione peroxidase activities did not differ (P b 0.05) between groups. Also, LV levels of HSP 72 (inducible) and 73 (constitutive) did not differ (P b 0.05)( between lean and obese animals. Following an iron-stimulated oxidative challenge in vitro, TBARS concentration was signi®cantly greater (P`0.05) in LV of obese rats compared to the lean (mean 12.7 vs 16.7 nMolamg lipid). CONCLUSIONS: These results support the notion that obesity predisposes the myocardium to oxidative stress. However, the postulate that obesity is associated with elevated myocardial antioxidant enzyme activities and HSPs was only partially supported by these ®ndings.