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.
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.
Authors: Erik Ingelsson; Martin G Larson; Xiaoyan Yin; Thomas J Wang; James B Meigs; Izabella Lipinska; Emelia J Benjamin; John F Keaney; Ramachandran S Vasan Journal: J Clin Endocrinol Metab Date: 2008-05-20 Impact factor: 5.958
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Authors: Qi Sun; Rob M van Dam; James B Meigs; Oscar H Franco; Christos S Mantzoros; Frank B Hu Journal: Diabetes Date: 2009-12-03 Impact factor: 9.461