Leptin and Soluble Leptin Receptor Levels in Obese and Weight-Losing Individuals

To investigate soluble leptin receptor (sLR) in plasma, specific anti-sLR monoclonal antibodies were developed. Western blot analysis and size exclusion fractionation demonstrated sLR in plasma with a molecular mass of approximately 180,000. Next to this, the presence of sLR-leptin complexes in plasma was confirmed. Using the developed monoclonal antibodies, a specific sLR ELISA was developed, which measured in plasma both free and sLR bound to leptin. sLR appeared to inhibit leptin concentrations measured in four different leptin assays indicating that these assays primarily measure free leptin and underestimate the total leptin present in plasma. Furthermore, plasma levels of sLR and leptin were measured in 21 lean individuals and in 30 morbidly obese subjects before and 3, 6, and 12 months after gastric restrictive surgery. Preoperatively, leptin concentrations significantly correlated with body mass index (r = 0.796, P < 0.001). In contrast, sLR significantly inversely correlated with body mass index (r = -0.294, P < 0.05). In lean subjects, the molar ratio of free leptin to sLR was 1:1, whereas in morbidly obese subjects a ratio of 25:1 was found. After weight loss due to surgery, leptin levels rapidly decreased and sLR levels slowly increased to reach normal values at 12 months postoperatively. We conclude that sLR levels are significantly decreased, whereas leptin levels are significantly increased in morbidly obese subjects compared with lean individuals.