Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men. Genetic and pharmacological evidence.

J Lipid Res. 1999 Feb;40(2):229-34.

Hepatic lipase activity influences high density lipoprotein subclass distribution
in normotriglyceridemic men. Genetic and pharmacological evidence.

Grundy SM, Vega GL, Otvos JD, Rainwater DL, Cohen JC.

Center for Human Nutrition, University of Texas Southwestern Medical Center,
Dallas, TX, 75235-9052, USA.

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 HDL(2b) was significantly higher and HDL(3a)
was significantly lower in -514T homozygotes than in -514C homozygotes. No
differences were noted in the other HDL fractions (HDL(2a), HDL(3b), and
HDL(3c)). 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 (HDL(2b) and HDL(2a)). The plasma concentrations of the
smallest HDL subclasses (HDL(3b) and HDL(3c)) 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: