Surgical Caloric Restriction Ameliorates Mitochondrial Electron Transport Dysfunction in Obese Females

Background The authors examine the mitochondrial electron transport system (ETS) with regard to caloric restriction and body size in humans. Methods The study population included 59 morbidly obese (MO) female subjects with mean body mass index (BMI) 49.6 ± 1.7 and 40 age-matched previously morbidly obese patients with surgically-induced caloric restriction (SCR) and mean BMI 28.9 ± 1.1. ETS function in the 2 study groups were made by measuring their lymphocyte mitochondrial ETS complexes IIV activities and complex III binding kinetics. Linear regression analyses were used to analyze the interactions between ETS function and BMI, energy intake, and metabolic status. Results The MO, as compared to SCR, subjects had significantly (P < 0.01) higher ETS complexes II-IV activities (complex II = 20.4 ± 1.9 vs 15.3 ± 1.1, complex III = 129.4 ± 10.1 vs 72.3 ± 4.9, complex IV = 3.1 ± 0.3 vs 1.4 ± 0.1 nmol/mg/min for the MO vs SCR, respectively). ETS complexes activities were positively and significantly correlated with subjects’ BMI, carbohydrate caloric intake, and fasting plasma insulin levels. Michaelis-Menten kinetic analysis showed that the Km for ubiquinol-2 in complex III of MO patients was 2-fold greater than SCR values, reflecting an apparent reduction in substrate binding capacities producing a resistance to electron flow in the MO population. Caloric consumption, carbohydrate calories, insulin levels, and BMI were also each significantly (P < 0.05) and positively correlated with the Km of Complex III. Conclusions ETS function and efficiency are compromised by increasing BMI and caloric consumption in morbidly obese women, and caloric restriction may reduce the potential for excessive oxidative free radical generation via the ETS.