Obesity and Lipoprotein Metabolism

The presence of visceral obesity and insulin resistance cause the increase of circulating triglyceride-rich lipoproteins (TRL), which is evidenced by an increase in plasmatic concentrations of triglycerides, apolipoprotein (apo) C-III, B-100 and B-48 and a reduction in HDL-cholesterol.

In obese subjects, this increase in plasmatic triglycerides is basically due to an impairment of TRL clearance and to an increase in VLDL secretion. Visceral obesity is related to an increase in VLDL release and unactivation of lipoprotein lipase (LPL), the enzyme in charge of TRL hydrolysis. These effects are related to insulin resistance, since this hormone controls the VLDL and chylomicron (CM) metabolism. In insulin resistance, it is not possible to suppress the hepatic apo B production, which occurs in the normal state. Also, insulin resistance suppresses the expression of the LDL receptor, which is involved in CM uptake to the liver and increases the concentration of apo CIII, the lipoprotein lipse inhibitor. For this reason, obese subjects have a higher postpranciual triglyceride response, measured either as plasmatic triglycerides or as apo B48 and apo B100 and they show a slower CM clearance rate.

Plasmatic accumulation of CM remnants (CMr) involves a major risk of atherosclerosis development, because there is a greater likelyhood of interacting with macrophages and forming foam cells. The formation of these cells is part of the inflammatory process that takes place during the formation of the atheromatous plaque and increases the proinflammatory state. In this situation, macrophages release a number of proinflammatory substances, like adhesion molecules, cytokines and eicosanoids, some of them also released by adipocytes.

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