Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence

Scott M Grundy,Gloria L Vega,James D Otvos,David L Rainwater,Jonathan C Cohen

doi:10.1016/s0022-2275(20)33361-7

Abstract

Several studies have reported an inverse relationship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent analytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare HDL subclass distributions in 11 homozygotes for the −514C allele of hepatic lipase and in 6 homozygotes for the −514T allele. Mean hepatic lipase activity was 45 ± 15 mmol·l−1·hr−1 in −514C homozygotes and 20 ± 7 mmol·l−1·hr−1 in −514T homozygotes. Both analytical methods indicated that HDL2b was significantly higher and HDL3a was significantly lower in −514T homozygotes than in −514C homozygotes. No differences were noted in the other HDL fractions (HDL2a, HDL3b, and HDL3c). To determine the effects of increased hepatic lipase activity, 20 men were given the synthetic anabolic steroid, stanozolol. Stanozolol treatment increased hepatic lipase activity more than two-fold (38 ± 18 to 85 ± 25 mmol·l−1·hr−1), and markedly reduced the plasma concentrations of the larger HDL subclasses (HDL2b and HDL2a). The plasma concentrations of the smallest HDL subclasses (HDL3b and HDL3c) were unchanged by stanozolol treatment. Taken together, these genetic and pharmacological data indicate that variation in hepatic lipase activity has highly specific effects on the distribution of HDL subclasses in the circulation.—Grundy, S. M., G. L. Vega, J. D. Otvos, D. L. Rainwater, and J. C. Cohen. Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence. J. Lipid Res. 1999. 40: 229–234.

Highlights

Several studies have reported an inverse relationship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations
Hepatic lipase activity was significantly lower in the 6 men who were Ϫ514T homozygotes than in the 11 men who were Ϫ514C homozygotes (Table 1)
HDL is a heterogenous group of lipoproteins that differ in size and composition [27,28,29]

Summary

Introduction

Several studies have reported an inverse relationship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. Stanozolol treatment increased hepatic lipase activity more than two-fold (38 ؎ 18 to 85 ؎ 25 mmolиl؊1иhr؊1), and markedly reduced the plasma concentrations of the larger HDL subclasses (HDL2b and HDL2a). The plasma concentrations of the smallest HDL subclasses (HDL3b and HDL3c) were unchanged by stanozolol treatment Taken together, these genetic and pharmacological data indicate that variation in hepatic lipase activity has highly specific effects on the distribution of HDL subclasses in the circulation.—Grundy, S. Saarinen, and Nikkila [4] reported that hepatic lipase activity was inversely correlated with plasma concentrations of HDL2, but not HDL3 determined by ultracentrifugation. All of the clinical studies performed to date were based on correlations observed between two phenotypes, hepatic lipase activity and HDL subclass distribution. A correlation between hepatic lipase activity and plasma HDL size among unselected individuals may reflect the interactions of plasma triglyceride concentrations (or some other confounder) with both parameters

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