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.