New insights into cardiovascular disease risk in subjects with visceral obesity

Obese insulin resistant individuals often present with a dyslipidemic phenotype characterised by hypertriglyceridemia, low HDL cholesterol levels, essentially normal total- and LDL-cholesterol, but a propensity for smaller, denser LDL particles. We have reported that concentrations of chylomicrons are two to three folds greater than in age-matched lean controls. We have recently observed that in lean free-living subjects the flux of chylomicrons over a 12h period was just 25% greater in these subjects than basal chylomicron production. Constitutive secretion of chylomicrons appears to be of greater relevance to arterial exposure than postprandial fluctuations. Insulin critically regulates the metabolism of very low density lipoprotein (VLDL) and hence it would be expected that the hormone is also involved in the regulation of chylomicron metabolism. Impaired insulin action may therefore be responsible for the associated hyperchylomicronaemia. In this review we examine the hypothesis that insulin chronically modulates chylomicron metabolism and present evidence suggesting that hyperchylomicronaemia primarily results from impaired chylomicron production.