Abstract

Obesity, insulin resistance (IR) with hyperinsulinemia, and a dyslipoproteinemia characterized by reduced high-density lipoprotein 2 (HDL 2) cholesterol and elevated levels of small, dense low-density lipoprotein (LDL) particles are risk factors for coronary artery disease (CAD). The impact of obesity independent of hyperinsulinemia on the concentration and composition of small, dense LDL subfractions is uncertain. The aim of this study was to investigate the relationship between obesity indices, namely body mass index (BMI), skinfold measurements (SF), and waist to hip ratio (WHR), and LDL-subfraction particle concentration and composition in 200 healthy men without evidence of IR. A precise analysis of the concentration of lipids and apolipoproteins and the composition of very—low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and two HDL- and six LDL-subfraction particles was obtained using the technique of density-gradient ultracentrifugation. Dividing the individuals according to BMI showed that those with a BMI greater than 27 kg/m 2 had significantly lower HDL 2 cholesterol and apolipoprotein (apo) A-I and higher VLDL and IDL cholesterol and apo B concentrations than those with a BMI less than 25 kg/m 2. Regarding LDL particles, we found that men with a BMI above 25 kg/m 2 had significantly more small, dense LDL particles (d 1.044 to 1.063 g/mL) and correspondingly fewer medium, dense LDL particles (d 1.031 to 1.037 g/mL) than leaner men; those with a BMI above 27 kg/m 2 had the highest concentration of circulating small, dense LDL particles. These findings were not influenced by fasting insulin concentrations, IR, or WHR. This study showed that obesity (BMI > 25 kg/m 2 associated with significantly higher SF, percent body fat, and waist circumference) is an important factor for the expression of a more atherogenic LDL-subclass phenotype even in normoinsulinemia. Characteristic differences in composition of LDL-subfraction particles between lean and obese men underlie the role of body weight in the metabolism of LDL-subfraction particles.

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