Abstract

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients’ systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET’s dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.

Highlights

  • Generation of neutrophil extracellular traps (NETs) contributes to the effector function of neutrophils[1,2]

  • No significantly differences in the two groups were observed in the lipid profile

  • The concentration of MPO-DNA complexes was significantly associated to weight, body mass index, waist and hip circumferences, systolic and diastolic blood pressure and glycol-metabolic profile (Table 2)

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Summary

Healthy Controls

We have investigated whether byproducts of NETs generation/catabolism accumulate in the plasma of morbid obese patients, whether they correlate with the anthropometric and glyco-metabolic parameters of the patients. The study group consisted of 73 patients (24 males and 49 females) with morbid obesity (mean body mass index 45.5 kg/m2) eligible for sleeve gastrectomy were recruited. Patients with severe obesity were studied immediately before and one year after sleeve gastrectomy. Platelet-free plasma retrieved were aliquoted and stored at −80 °C until quantification of NETs. Blood sample was drawn in the morning after a 13-hour fast. Human platelet-free plasma samples were placed in the coated wells with peroxidase-conjugated anti-DNA antibodies (clone MCA-33, from the cell death detection ELISA kit) following the kit instructions. Mann-Whitney U test was used to compare the means of two unmatched groups variables (e.g. healthy and obese subjects). The difference of different variables at time 0 and after intervention was calculated (delta, Δ)

Results
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Author Contributions
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