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

• Published in: Clinical biochemistry Vol. 36; no. 6; pp. 421 - 429
• Main Authors: Rashid, Shirya, Watanabe, Takehiko, Sakaue, Taro, Lewis, Gary F
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2003
• Subjects: Animals; Apolipoprotein A-I; Apolipoprotein A-I - blood; Apolipoprotein A-I - metabolism; Atherosclerotic cardiovascular disease; Cholesterol Esters - blood; Cholesterol Esters - metabolism; Cholesterol, HDL - blood; Cholesterol, HDL - metabolism; Cholesteryl ester transfer protein; Hepatic lipase; High density lipoprotein (HDL); Humans; Hypertriglyceridemia; Hypertriglyceridemia - blood; Hypertriglyceridemia - drug therapy; Hypertriglyceridemia - metabolism; Insulin Resistance - physiology; Insulin resistance syndrome; Lipase - metabolism; Lipoprotein Lipase - metabolism; Lipoproteins, HDL - blood; Lipoproteins, HDL - metabolism; Lipoproteins, HDL - pharmacology; Liver - enzymology; Metabolic syndrome; Particle Size; Triglycerides - metabolism; Triglycerides - pharmacology; Type 2 diabetes; Type 2 diabetes; Atherosclerotic cardiovascular disease; Hypertriglyceridemia; Apolipoprotein A-I; High density lipoprotein (HDL); Insulin resistance syndrome; Metabolic syndrome; Hepatic lipase; Cholesteryl ester transfer protein
• ISSN: 0009-9120; 1873-2933
• 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.