Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.
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.
Rashid
Shirya
S
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
Watanabe
Takehiko
T
Sakaue
Taro
T
Lewis
Gary F
GF
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008049:Lipase / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D010316:Particle Size; D014280:Triglycerides / Q000378:metabolism / Q000494:pharmacology
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; C034396:HDL-triglyceride; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase; D008071:Lipoprotein Lipase