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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1225.)
© 2008 American Heart Association, Inc.

Brief Review

Overproduction of Very Low–Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome

Martin Adiels; Sven-Olof Olofsson; Marja-Riitta Taskinen; Jan Borén

From the Sahlgrenska Center for Cardiovascular and Metabolism Research, Wallenberg Laboratory for Cardiovascular Research and the Department of Molecular and Clinical Medicine (M.A., S.-O.O., J.B.), The Sahlgrenska Academy at University of Gothenburg, Sweden; and the Division of Diabetes (M.-R.T.), University of Helsinki, Finland.

Correspondence to Martin Adiels Wallenberg Laboratory Sahlgrenska University Hospital 41345 Gothenburg, Sweden. E-mail Martin.adiels{at}wlab.gu.se

Series Editor: Marja-Riitta Taskinen
Metabolic Syndrome and Atherosclerosis
ATVB In Focus

Preview Brief Reviews in this Series:

•Grundy, SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. 2008;28:629–636.
•Barter PJ, Rye KA. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:39–46.
•Kotronen A, Yki-Järvinen. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:27–38.
•Gustafson B, Hammarstedt A, Andersson CX, Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:2276–2283.
•Rigamonti E, Chinetti-Gbaguidi G, Staels B. Regulation of macrophage functions by PPAR-, PPAR-, and LXRs in mice and men. Arterioscler Thromb Vasc Biol. 2008;28:1050–1059.
•Kockx M, Jessup W, Kritharides L. Regulation of endogenous apolipoprotein E secretion by macrophages. Arterioscler Thromb Vasc Biol. 2008;28:1060–1067.

Insulin resistance is a key feature of the metabolic syndrome and often progresses to type 2 diabetes. Both insulin resistance and type 2 diabetes are characterized by dyslipidemia, which is an important and common risk factor for cardiovascular disease. Diabetic dyslipidemia is a cluster of potentially atherogenic lipid and lipoprotein abnormalities that are metabolically interrelated. Recent evidence suggests that a fundamental defect is an overproduction of large very low–density lipoprotein (VLDL) particles, which initiates a sequence of lipoprotein changes, resulting in higher levels of remnant particles, smaller LDL, and lower levels of high-density liporotein (HDL) cholesterol. These atherogenic lipid abnormalities precede the diagnosis of type 2 diabetes by several years, and it is thus important to elucidate the mechanisms involved in the overproduction of large VLDL particles. Here, we review the pathophysiology of VLDL biosynthesis and metabolism in the metabolic syndrome. We also review recent research investigating the relation between hepatic accumulation of lipids and insulin resistance, and sources of fatty acids for liver fat and VLDL biosynthesis. Finally, we briefly discuss current treatments for lipid management of dyslipidemia and potential future therapeutic targets.

Diabetic dyslipidemia is a cluster of potentially atherogenic lipid and lipoprotein abnormalities that are metabolically interrelated. Recent evidence suggests that a fundamental defect is an overproduction of large very low–density lipoprotein (VLDL) particles. Here, we review the pathophysiology of VLDL biosynthesis and metabolism in the metabolic syndrome.

Key Words: apolipoprotein B • VLDL₁ • insulin resistance • metabolic syndrome • nonalcoholic fatty liver disease • stable isotopes • kinetics

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