Abstract: | Objective: In obesity, plasma leptin is high and soluble leptin receptor (sOb‐R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb‐R concentration and the bound‐free ratio of leptin. Research Methods and Procedures: sOb‐R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle‐aged obese or overweight men. Results: Concentration of sOb‐R and soluble receptor‐bound fraction of leptin were lowest in the highest tertile of HOMA‐IR. sOb‐R and the bound‐free ratio of leptin correlated with HOMA‐IR, leptin concentration, and waist‐to‐hip ratio independently of age, BMI, and fat mass. Leptin and waist‐to‐hip ratio were the sole independent determinants of sOb‐R concentration, and BMI, HOMA‐IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb‐R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb‐R concentration and a lower fraction of bound leptin in men with the MS. Discussion: IR and abdominal obesity are associated with low sOb‐R concentration and low bound‐free ratio of leptin independent of fat mass. Low sOb‐R concentration and low bound‐free ratio of leptin segregate with components of the MS. We suggest that low sOb‐R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS. |