Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects
Vinagre Carmen G1,2, Freitas Fatima R1, de Mesquita Carlos H3, Vinagre Juliana C1, Mariani Ana Carolina2, Kalil-Filho Roberto1, Maranhão Raul C1,4,*
1Heart Institute (InCor) of Medical School Hospital, University of São Paulo, São Paulo, Brazil. 2University of Santo Amaro, São Paulo, Brazil 3Institute of Nuclear Research, University of São Paulo, São Paulo, Brazil 4Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
Dietary fats absorbed in the intestine are transported in the circulation as chylomicrons and remnants that have atherogenic potential. Although postprandial lipidemia is increased in older subjects, the specific chylomicron metabolism has not been explored in older subjects nor compared to young subjects, which is the focus of this study. After a 12 h fast, artificially-made emulsions similar to lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides were intravenously injected in 23 older (66±4 years) and 20 young (24±3 years) subjects. Sequential blood samples were collected to determine fractional clearance rates (FCR, in min-1) by compartmental analysis. Older subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl-ester FCR was lower in older subjects compared to the young (p=0.0001). The emulsion triglyceride FCR did not differ in the two groups. Tested in vitro, however, the lipolysis of the emulsion triglycerides was less intense in the older than in the young subjects. As delayed removal of remnants, indicated by the pronouncedly smaller cholesteryl ester FCR, is related to the presence of cardiovascular diseases, this can be a risk factor which could accelerate atherogenic complications occurring in aged subjects
Table 1 Plasma lipids and in vitro lipolysis measured in subjects with age under 30 years (young group) and with more than 60 years (older group).
Figure 1. Kinetic model employed for chylomicron-like emulsion metabolism in vivo
The observed data (compartments C1 and C2) present a biexponential curve. Compartments C1- C4 represent kinetics of 14C-cholesteryl oleate (14C-CE). Compartments C5 - C8 represent kinetics of 3H-triglycerides (3H-TG). Compartments C1 and C5 represent emulsion after plasma injection. Compartments C2 and C6 represent emulsion after redistribution. Compartments C3 and C7 correspond extra-vascular space, mainly the liver, and C4 and C8 the emulsion labeled lipids recirculation. The constants ki,j (min-1) represent the fractional catabolic rate (FCR) or transfer from compartment j to compartment i over time. k3,1 and k7,5 - fraction of injected emulsion that is removed directly from plasma by the liver and other tissues. k2,1 and k6,5 - emulsion transfer rates to a complex plasma lipoprotein pool. k3,2 and k7,6 - removal from the plasma of the emulsion mainly by the liver. k4,3 and k 8,7 - emulsion transfer rates to VLDL (labeled lipids recirculation). k3,4 and k7,8 - recirculated lipids removal by the liver. k0,4 and k0,8 - output of labeled lipids from the body.
k2,1 = k6,5
k3,1 = k7,5
14C-CE FCR (min-1)
3H-TG FCR (min-1)
Table 2 Kinetics and compartmental analysis parameters in subjects with age under 30 years (young group) and with more than 60 years (older group).
Figure 2. Plasma decay curve of the emulsion cholesteryl esters (A) and triglycerides (B) in healthy subjects with age under 30 years (young) and those with age above 60 years (older). The chylomicron-like emulsion labeled with the radioactive lipids was injected intravenously after a 12 hour fast. Plasma samples were taken at regular intervals over 60 minutes to determine the radioactivity remaining in the plasma in a scintillation solution.
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