Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans

OBJECTIVE: Leptin plays a major role in the regulation of body weight. It circulates in both free and bound form. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. In the present study, we measured the soluble leptin receptor (SLR) levels in lean and obese humans. We investigated the relationship between plasma SLR levels, plasma leptin levels and the degree of obesity. We also examined whether SLR concentrations could be modulated by fat mass loss induced by a 3 month weight-reducing diet. SUBJECTS: A total of 112 obese (age 18 -50 y; body mass index (BMI) 30 - 44 kg/m(2); 23 men and 89 women), 38 overweight (age 19-48y; BMI 25-29 kg/m(2); 10 men and 28 women) and 63 lean (age 18-50y; BMI 17-24 kg/m(2); 16 men and 47 women) humans. MEASUREMENTS: A direct double monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) was used for the quantitative measurement of the soluble human leptin receptor. Leptin was measured by radioimmunoassay (RIA). Body composition was assessed by biphotonic absorptiometry DEXA (dual energy X-ray absorptiometry). RESULTS: We observed that the SLR is present in human plasma (range 10-100 ng/ml). SLR levels were lower in obese and overweight than lean subjects (28.7 +/- 8.8, 40.2 +/- 14.9, 51.2 +/- 12.5 ng/ml, respectively) and were inversely correlated to leptin and percentage of body fat (r= - 0.74 and r= - 0,76; respectively; P < 0.0001). The ratio of circulating leptin to SLR was strongly related to the percentage of body fat (r= 0.91; P < 0.0001). Interestingly a gender difference was observed in SLR levels, which were higher in obese and overweight men than in obese and overweight women. In obese subjects after a 3 month low-calorie diet, SLR levels increased in proportion to the decrease in fat mass. In the gel filtration profile, SLR coeluted exactly with the bound leptin fractions. CONCLUSION: Obesity, in humans is associated with decreasing levels of the circulating soluble leptin receptor (SLR). The relationship of SLR with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects.