Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects

Objectives: Proprotein 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 methods: We assessed the extent to which plasma PCSK9 levels are determined by resistin in individuals with varying degrees of obesity.

Results: In 80 subjects (35 women; no diabetes mellitus) with body mass index ranging from 19.4 to 40.4 kg/m(2), 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/m(2) (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/m(2) (n=42), PCSK9 was unrelated to resistin (r=-0.064, p=0.69).

Conclusions: This 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.