title: Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shirya
authors.initials: S
authors.lastname: Rashid
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Taro
authors.initials: T
authors.lastname: Sakaue
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: 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
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; C034396:HDL-triglyceride; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase; D008071:Lipoprotein Lipase