Weight Loss in Combination With Physical Activity Improves Endothelial Dysfunction in Human Obesity

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Abstract
OBJECTIVE—To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30–46 years, with BMI 30–43 kg/m2. RESEARCH DESIGN AND METHODS—Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 μg · ml−1 · min−1) and sodium nitroprusside (0.8, 1.6, and 3.2 μg · ml−1 · min−1). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity. RESULTS—We observed a significant reduction in BMI (from 33.1 ± 4.2 to 27.5 ± 4.5 kg/m2, −16.9%, P < 0.0001) and in waist circumference (from 108.2 ± 12.1 to 96.8 ± 12.9 cm, −10.5%, P < 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 ± 2.8 to 12.9 ± 3.4 ml · 100 ml−1 of tissue · min−1 kg/m2 (P < 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation. CONCLUSIONS—Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects.