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

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 HLL(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.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalJournal of Lipid Research
Volume40
Issue number2
StatePublished - Feb 1999

Fingerprint

HDL Lipoproteins
Lipase
Pharmacology
Liver
Homozygote
Stanozolol
Plasmas
Testosterone Congeners
Alleles
Electrophoresis
HDL Cholesterol
Magnetic Resonance Spectroscopy
Gels

Keywords

  • Hepatic lipase
  • High density lipoprotein
  • Nuclear magnetic resonance
  • Particle size
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: Genetic and pharmacological evidence",
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 HLL(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.",
keywords = "Hepatic lipase, High density lipoprotein, Nuclear magnetic resonance, Particle size, Polymorphism",
author = "Grundy, {Scott M} and Vega, {Gloria L} and Otvos, {James D.} and Rainwater, {David L.} and Cohen, {Jonathan C}",
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T1 - Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men

T2 - Genetic and pharmacological evidence

AU - Grundy, Scott M

AU - Vega, Gloria L

AU - Otvos, James D.

AU - Rainwater, David L.

AU - Cohen, Jonathan C

PY - 1999/2

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N2 - 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 HLL(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.

AB - 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 HLL(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.

KW - Hepatic lipase

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KW - Nuclear magnetic resonance

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