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

Several studies have reported an inverse relationship between hepatic lipas e activity and plasma high density lipoprotein (HDL) cholesterol concentrat ions. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distributi on of HDL subclasses. Two independent analytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare HDL subcla ss distributions in 11 homozygotes for the -514C allele of hepatic lipase a nd 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 homozygote s than in -514C homozygotes. No differences were noted in the other HDL fra ctions (HDL2a, HDL3b, and HDL3c). To determine the effects of increased hep atic lipase activity, 20 men were given the synthetic anabolic steroid, sta nozolol. Stanozolol treatment increased hepatic Lipase activity more than t wo-fold (38 +/- 18 to 85 +/- 25 mmol.l(-1).hr(-1)), and markedly reduced th e plasma concentrations of the larger HDL subclasses (HDL2b and HDL2a). The plasma concentrations of the smallest HDL subclasses (HDL3b and HDL3c) wer e unchanged by stanozolol treatment. Taken together, these genetic and phar macological data indicate that variation in hepatic lipase activity has hig hly specific effects on the distribution of HDL subclasses in the circulati on.