Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study

Abstract

Little is known about the mechanisms underlying the cardioprotective effect of Roux en-Y gastric bypass (RYGB) surgery. Therefore, the aim of the present study was to investigate whether weight loss associated with RYGB improves the oxidative status of leukocytes and ameliorates subclinical atherosclerotic markers. This is an interventional study of 57 obese subjects who underwent RYGB surgery. We determined biochemical parameters and qualitative analysis of cholesterol, leukocyte and systemic oxidative stress markers -superoxide production, glutathione peroxidase 1 (GPX1), superoxide dismutase (SOD) activity and protein carbonylation-, soluble cellular adhesion molecules -sICAM-1 and sP-selectin-, myeloperoxidase (MPO) and leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion. RYGB induced an improvement in metabolic parameters, including hsCRP and leukocyte count (p < 0.001, for both). This was associated with an amelioration in oxidative stress, since superoxide production and protein carbonylation were reduced (p < 0.05 and p < 0.01, respectively) and antioxidant systems were enhanced (GPX1; p < 0.05 and SOD; p < 0.01). In addition, a significant reduction of the following parameters was observed one year after RYGB: MPO and sICAM (p < 0.05, for both), sPselectin and pattern B of LDL particles (p < 0.001, for both), and rolling flux and adhesion of leukocytes (p < 0.05 and p < 0.01, respectively). Our results suggest that patients undergoing RYGB benefit from an amelioration of the prooxidant status of leukocytes, metabolic outcomes, and subclinical markers of atherosclerosis.

Keywords: atherosclerosis; bariatric surgery; leukocyte-endothelium interactions; obesity; oxidative stress.

Figure 1

Evaluation of prooxidant/antioxidant responses and oxidative stress markers in obese patients before and 12 months after RYGB intervention. (A) Superoxide production in leukocytes, measured as arbitrary units of DHE fluorescence and their representative fluorescence microscopy 100× images (n = 17). (B) Levels of GPX1 protein expression in leukocytes and representative Western blot images (n = 20). (C) MPO levels (n = 46) and (D) SOD activity in serum. (E) Carbonyl groups in serum proteins (n = 14). Data are represented as the mean + SE. * p < 0.05 ** p < 0.01 when compared using a paired Student’s t-test. RYGB: Roux-en-Y gastric bypass; DHE: Dihydroethidium; RFU: Relative fluorescence units; GPX1: Glutathione peroxidase 1; MPO: Myeloperoxidase; SOD: Superoxide dismutase.

Figure 2

Evaluation of leukocyte-endothelial cell interactions and serum levels of CAMs in obese patients before and 12 months after RYGB intervention. (A) Rolling flux, measured as cells per minute (n = 24). (B) Leukocyte rolling velocity, expressed as µm/s (n = 24). (C) Leukocyte adhesion, expressed as cells/mm² (n = 24). Serum levels of (D) sICAM-1 (n = 46) and (E) sP-selectin (n = 46). Data are represented as the mean + SE. * p < 0.05, ** p < 0.01, *** p < 0.001 when compared using a paired Student’s t-test. CAMs: Cellular adhesion molecules; RYGB: Roux-en-Y gastric bypass; sICAM-1: Soluble intracellular adhesion molecule; sP-selectin: Soluble platelet selectin.

Figure 3

Cholesterol subfractions in obese patients before and 12 months after RYGB intervention, determined by the Quantimetrix Lipoprint^® system. (A) LDL electrophoretic profiles are expressed as the percentage of patients (n = 25) displaying a particular LDL pattern. Patterns refer to the size of LDL particles, as follows: Pattern A (cut-off diameter ≥ 268 Å); Intermediate Pattern (cut-off diameter 264–267 Å) and Pattern B (cut-off diameter ≤ 265 Å). (B) HDL profile, expressed as the percentage of patients (n = 25) displaying a particular HDL pattern: Large, intermediate, or small. Data are represented as a percentage of LDL patterns or mean + SE. *** p < 0.001 when proportions were compared using a X² test or a paired Student’s t-test. RYGB: Roux-en-Y gastric bypass; LDL: Low-density lipoprotein; HDL: High-density lipoprotein.