Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity

Clin Biochem. 2003 Sep;36(6):421-9. doi: 10.1016/s0009-9120(03)00078-x.


Hypertriglyceridemia, low plasma concentrations of high density lipoproteins (HDL) and qualitative changes in low density lipoproteins (LDL) comprise the typical dyslipidemia of insulin resistant states and type 2 diabetes. Although isolated low plasma HDL-cholesterol (HDL-c) and apolipoprotein A-I (apo A-I, the major apolipoprotein component of HDL) can occur in the absence of hypertriglyceridemia or any other features of insulin resistance, the majority of cases in which HDL-c is low are closely linked with other clinical features of insulin resistance and hypertriglyceridemia. We and others have postulated that triglyceride enrichment of HDL particles secondary to enhanced CETP-mediated exchange of triglycerides and cholesteryl ester between HDL and triglyceride-rich lipoproteins, combined with the lipolytic action of hepatic lipase (HL), are driving forces in the reduction of plasma HDL-c and apoA-I plasma concentrations. The present review focuses on these metabolic alterations in insulin resistant states and their important contributions to the reduction of HDL-c and HDL-apoA-I plasma concentrations.

Publication types

  • Review

MeSH terms

  • Animals
  • Apolipoprotein A-I / blood
  • Apolipoprotein A-I / metabolism
  • Cholesterol Esters / blood
  • Cholesterol Esters / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / metabolism
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy
  • Hypertriglyceridemia / metabolism*
  • Insulin Resistance / physiology*
  • Lipase / metabolism*
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, HDL / pharmacology
  • Liver / enzymology*
  • Particle Size
  • Triglycerides / metabolism
  • Triglycerides / pharmacology


  • Apolipoprotein A-I
  • Cholesterol Esters
  • Cholesterol, HDL
  • HDL-triglyceride
  • Lipoproteins, HDL
  • Triglycerides
  • Lipase
  • Lipoprotein Lipase