Lack of a relationship between plasma PCSK9 concentrations and hepatic lipoprotein kinetics in obese people

Obesity is associated with unfavorable alterations in plasma lipid concentrations. Data obtained from studies in cultured cells and rodent models show that Protein Convertase Subtilisn/Kexin 9 (PCSK9), a secreted protein that leads to degradation of LDL receptors in the liver, is an important regulator of plasma LDL cholesterol concentrations. Recent evidence suggests that PCSK9 may also regulate the very low density lipoprotein (VLDL) receptor expression and VLDL-triglyceride (TG) metabolism. The purpose of this study was to determine whether circulating PCSK9 concentrations are correlated with VLDL-triglyceride kinetics in obese people. Plasma PCSK9 concentration and VLDL-TG kinetics were evaluated in 39 nondiabetic, obese subjects (body mass index 36.9 +/- 4.3 kg/m(2)). Body composition was assessed by using dual-energy x-ray absorptiometry, and VLDL-TG kinetics were assessed by using stable isotopically labeled tracer infusion. We found that plasma PCSK9 concentrations correlated significantly with percent body fat Cr = 0.322, P = 0.046) and serum LDLcholesterol concentrations (r = 0.333, P = 0.036), but not with VLDL-TG secretion rate (r = 0.083, P = 0.614) or clearance rate (r = 0.032, P = 0.845). These data suggest that PCSK9 is likely involved in LDL-cholesterol metabolism, but it is not a clinically important regulator of VLDL kinetics in obese individuals. (Translational Research 2011;158:302-306)