Nitric oxide production is paradoxically decreased after weight reduction surgery in morbid obesity patients

Obesity is associated with vascular endothelial cell dysfunction (ECD). Studies on nitric oxide (NO) production of vascular system in these subjects may help delineate the pathogenesis of obesity-associated ECD. In this study, we recruited 69 severely obese patients who were treated with gastric partition surgery for weight reduction and 69 matched healthy controls for comparison. The following parameters were obtained in the healthy control subjects and in the obese subjects both before and after gastric partition surgery: body mass index, blood pressure, serum lipids, high sensitivity C-reactive protein (hs-CRP), adiponectin, total nitrite and nitrate (NO(x)), and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), and insulin resistance index (as measured by homeostasis model assessment (HOMA-IR). At baseline, serum lipids, glucose, insulin, hs-CRP and 8-iso-PGF2alpha and HOMA-IR were all higher while adiponectin lower in the obese group than in the control group. The serum NO(x) levels were not different between the two groups. In the obese subjects, the adiponectin levels were significantly elevated but NO(x) markedly decreased after surgery. All other measurements, except for systolic blood pressure, were decreased after surgery. For healthy controls, the serum NO(x) levels were negatively associated with HOMA-IR and positively associated with serum adiponectin levels as analyzed by multiple linear regression analysis. In obese patients, the baseline serum NO(x) was positively associated with the serum TG levels. The changes of serum NO(x) levels after weight reduction surgery were positively associated with the changes of body mass index and serum TG levels. These observations suggested that, in the extremely obese patients, there might be excessive production and/or inactivation of NO and, after weight reduction surgery, the NO production was down-regulated. In conclusion, in the severely obese patients, the apparently normal NO production might be due to over-expression of iNOS. After gastric partition surgery, the NO production was significantly decreased which might be reflecting the usual status of NO production in obese subjects. The positive correlation between NO(x) and serum TG level might suggest that the metabolism of TG plays a role in the regulation of NO production.