Abstract

Introduction: Roux-en-Y gastric bypass (RYGB) reduces cardiometabolic risk through different potential mechanisms. High density lipoprotein cholesterol (HDL-C) changes might explain part of this benefit. Hypothesis: We assessed the effect of RYGB on HDL vasoprotective properties in comparison with a hypocaloric diet-induced weight loss. Methods: HDL was isolated from serum of obese patients (BMI > 35 kg/m2) before and 6 months after RYGB (n=32) or diet (n=32). In endothelial cells stimulated with HDL, we quantified nitric oxide (NO) production by DAF-2 fluorescence and paraoxonase-1 antioxidant activity (PON-1). Total cholesterol, low density lipoprotein (LDL-C), HDL-C, and triglycerides (TG) as well as glucose plasma fasting levels were measured. Results: At baseline there was no significant difference in mean body weight (BW) and BMI between RYGB and diet patients (119.9 Kg; 42kg/m2 vs. 110.9 kg; 37.4 kg/m2, respectively, p=0.06). At 6 months, BW and BMI were not different (RYGB: 94kg; 33 kg/m2; diet: 99kg; 33.4 kg/m2, p=ns). In both groups, mean total cholesterol and TG were reduced; LDL-C decreased only after RYGB. Total HDL-C increased 6 months after both interventions (RYGB: 1.2±0.5 baseline vs 1.3±0.4 after 6months; diet 1.1±0.25 baseline vs 1.3±0.3 after 6months, p<0.05). However, only RYGB improved the vasoprotective HDL-stimulated NO production (RYGB: 234.2±178.0 vs diet 98.8±76.4 arbitrary units, p<0.0001) and HDL-associated PON-1 activity (RYGB: 40% vs diet: 9% increase compared to baseline; p<0.0001). Fasting glucose levels improved in both groups and were not different at 6 months between the two interventions. Conclusions: Our study shows that although HDL concentration increased after RYGB and diet-induced BW loss, only RYGB restored endothelial protective HDL properties even though patients were still obese. This suggests that BW loss is not sufficient or critical to improve the protective properties of HDL, unless accompanied by yet unknown surgery-specific effects.

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