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Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects
Authors:Arjan J Kwakernaak  Gilles Lambert  Robin PF Dullaart
Institution:1. Physics Department, B C College, Asansol 713304, West Bengal, India;2. Physics Department, Burdwan University, Burdwan 713104, West Bengal, India;1. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy;2. Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland;3. Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland;4. Clinic of Emergency Medicine, Department of Emergency Medicine, University of Genoa and Ospedale Policlinico San Martino, 10 Largo Rosanna Benzi, 16132 Genoa, Italy;5. Vascular and Endovascular Surgery Unit, Department of Surgery, University of Genoa and Ospedale Policlinico San Martino, 10 Largo Rosanna Benzi, 16132 Genoa, Italy;6. Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy;7. Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy
Abstract:ObjectivesProprotein convertase subtilisin-kexin type 9 (PCSK9), a key regulator of low density lipoprotein receptor expression, has recently been reported to be upregulated by resistin in HepG2 cells and human primary hepatocytes. Whether this translates into a positive relationship of plasma PCSK9 with resistin levels in humans with varying degrees of obesity is unknown.Design and methodsWe assessed the extent to which plasma PCSK9 levels are determined by resistin in individuals with varying degrees of obesity.ResultsIn 80 subjects (35 women; no diabetes mellitus) with body mass index ranging from 19.4 to 40.4 kg/m2, plasma PCSK9 levels were not positively related to resistin (r = ? 0.161, p = 0.154). Despite positive correlations of non-high density lipoprotein cholesterol (r = 0.378, p < 0.001), low density lipoprotein (r = 0.292, p < 0.01) and apolipoprotein B (apoB) (r = 0.266, p < 0.05) with PCSK9, none of these apolipoprotein (apo) B-containing lipoprotein measures was positively related to resistin (p > 0.10 for all). In subjects with BMI < 25.0 kg/m2 (n = 38), PCSK9 was even inversely related to resistin (r = ? 0.322, p = 0.049), and this relationship remained present after controlling for either leptin (p = 0.027) or insulin resistance (P = 0.031). In subjects with BMI  25.0 kg/m2 (n = 42), PCSK9 was unrelated to resistin (r = ? 0.064, p = 0.69).ConclusionsThis study demonstrates that there is no positive association of plasma PCSK9 with resistin in lean and moderately obese individuals. Our data question whether circulating resistin is a physiologically important determinant of higher PCSK9 levels.
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