The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity

OBJECTIVE: The increased cardiovascular (CV) disease risk in patients with morbid obesity (MO) cannot be fully explained by traditional CV risk factors. Activation of the receptor of Advanced Glycation Endproducts (RAGE) leads to inflammation via the NF kappa beta (nuclear factor kappa beta) pathway. The soluble form of RAGE (sRAGE), which is present in plasma, can bind to ligands of RAGE and avoids interaction of RAGE with proinflammatory ligands. We investigated sRAGE levels in patients with MO and compared them with healthy lean controls (CO), before and after bariatric surgery. DESIGN: We conducted a cross-sectional study and a 24-month longitudinal study. SUBJECTS: We included 85 patients (mean age: 41 +/- 12 years; mean body mass index (BMI): 45.4 +/- 7.9 kg m(-2)) with MO in comparison with 40 CO (mean age: 42 +/- 13 years; mean BMI: 26.0 +/- 5.5 kg m(-2)). All patients were investigated before and 2 years after bariatric surgery. Apart from weight and CV risk markers (blood pressure, lipids), a glucose tolerance test (75 g), renal and inflammation parameters were assessed. sRAGE levels were assessed by a commercial ELISA. To investigate the associations of the observed reductions of values, delta (Delta) of parameters were calculated. RESULTS: Patients with MO had significant lower sRAGE levels than CO: 1010 +/- 514 vs 1501 +/- 674 pg ml(-1); P<0.001. In the longitudinal study, sRAGE levels increased significantly after bariatric surgery from 1010 +/- 514 to 1261 +/- 710 pg ml(-1); P = 0.008. In the correlation analysis, Delta sRAGE levels were associated with Delta 1-h and Delta 2-h postprandial glucose, Delta fasting insulin, Delta 2-h postprandial insulin, Delta HOMA (homeostatic model assessment)-insulin resistance (Delta HOMA-IR), Delta gamma-glutamyl transferase and Delta triglycerides. In a multivariate model, Delta 1-h and Delta 2-h postprandial glucose, Delta 2-h postprandial insulin and Delta HOMA-IR predicted Delta sRAGE. CONCLUSION: Patients with MO have significantly lower sRAGE levels compared with non-obese CO, but sRAGE levels increase significantly after weight loss induced by bariatric surgery. As high sRAGE levels inhibit the activation of inflammatory pathways, our results might help understand the beneficial effects of bariatric surgery regarding CV morbidity and mortality. International Journal of Obesity (2012) 36, 1412-1417; doi:10.1038/ijo.2012.107; published online 17 July 2012