Insulin Resistance and Lipid Disorders

Roberto Miccoli; Cristina Bianchi; Giuseppe Penno; Stefano Del Prato

Disclosures

Future Lipidology. 2008;3(6):651-664. 

In This Article

Pathophysiology of Dyslipidemia Associated with Insulin Resistance

Altered metabolism of TG-rich lipoproteins is crucial in the pathophysiology of dyslipidemia associated with insulin resistance. Alterations include increased hepatic secretion, as well as impaired clearance of VLDL and intestinally derived chylomicrons.[21] An important consequence of slow clearance is the persistence in the circulation of both VLDL, postprandial chylomicrons and partially metabolized remnant particles (Figure 1). Remnants include cholesterol-enriched intermediate-density lipoproteins that have been shown to confer high atherogenic risk in experimental animal models as well as in man.[22]

Figure 1.

In insulin-resistance states, enhanced lipolysis and increased fatty acid flux from adipose tissue, hypersecretion and hypocatabolism of CM and VLDL remnants, and DNL are three major sources of TG, the main substrate regulating ApoB secretion as VLDL. In the presence of increased VLDL in the plasma and normal activity of the plasma protein CETP, VLDL TG can be exchanged for LDL- and HDL-cholesterol. This exchange produces LDL particles enriched in TG, which are rapidly lipolyzed by HL, leaving smaller, denser LDL particles. The TG-rich HDL particle can undergo further modification, including hydrolysis of its TG by HL, which leads to the dissociation of the structurally important protein ApoA-I. The free ApoA-I in plasma is cleared more rapidly than ApoA-I associated with HDL particles and the number of HDL particles will be reduced. In addition, reduced cholesterol efflux from cells, in combination with lower availability of precursors of nascent HDL, contributes to decreased HDL-cholesterol concentrations.

ABCA1 = Adenosine triphosphate-binding cassette transporter A1; Apo = Apolipoprotein; CE = Cholesterol ester; CETP = Cholesteryl ester transfer protein; CM =Chlyomicron; DNL = De novo hepatic lipogenesis; HL = Hepatic lipase; HSL = Hormone-sensitive lipase; LCAT = Lecithin =cholesterol acyltransferase; LPL = Lipoprotein lipase; MTP = Microsomal TG protein; NEFA = Nonesterified free fatty acid; SR-B1 = Scavenger receptor B1; TG = Triglyceride.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....