Delayed clearance of triacylglycerol-rich lipoprotein particles from intestinal (chylomicrons) and hepatic (VLDL) origins is emerging as a leading risk factor for atherosclerosis, however, it is unclear whether hypertriglyceridemia is a defect in secretion, hydrolysis, and/or particle uptake. As a result, tracer studies that can quantify rate processes, such as VLDL synthetic rates or chylomicron clearance rates, have emerged as a high scientific priority. Beta-carotene (beta-CAR) and vitamin A are lipid soluble nutrients whose fates are linked to their lipoprotein carriers. Accordingly, investigations on the fate of these compounds reveal information on the underlying structure and dynamics of the lipoprotein system, which in turn, clarifies the role of carotenoids and retinoids in health and disease. To establish the role of beta-CAR and retinoids in chemoprevention and atherosclerosis in the context of lipid transporting systems, 14C labeled beta-CAR and retinyl palmitate is consumed and the concentration time-course of the label is determined into lipoprotein subclasses and excretory fluids (urine and stool). Such in vivo investigations are facilitated by Accelerator Mass Spectrometry (AMS): AMS can quantify attomoles (10-18 moles) or attoCuries of 14C-labeled compounds from milligram-sized biochemical samples enabling studies at relevant dietary levels (7, 8). Our long-range goal is to describe the dynamic behavior of beta-CAR and vitamin A metabolism in humans, ultimately developing a predictive model of human physiological that is sensitive to the genetic and environmental determinants of disease initiation and progression. In pursuit of this goal, our immediate objectives are to elucidate the uptake and distribution of 14C labeled beta-CAR and vitamin A among human lipoproteins following a true tracer dose. Emphasis will be given to the differential distribution of labeled beta-CAR and vitamin A and their metabolites among the intestinal and hepatogeneous triacylglyceride-rich (TRL) lipoproteins subclasses in the postprandial phase; in doing so, aspects of the chemical and anatomical pathways of absorption for these compound will be explained.
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