Abstract
Approximately 25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues. Little is known about physiologic factors important to this uptake. We hypothesized that lipoprotein lipase (LpL) contributes to extrahepatic clearance of chylomicron vitamin A. To investigate this, [3H]retinyl ester-containing rat mesenteric chylomicrons were injected intravenously into induced mutant mice and nutritionally manipulated rats. The tissue sites of uptake of 3H label by wild type mice and LpL-null mice overexpressing human LpL in muscle indicate that LpL expression does influence accumulation of chylomicron retinoid. Skeletal muscle from mice overexpressing human LpL accumulated 1.7- to 2.4-fold more 3H label than wild type. Moreover, heart tissue from mice overexpresssing human LpL, but lacking mouse LpL, accumulated less than half of the 3H-label taken up by wild type heart. Fasting and heparin injection, two factors that increase LpL activity in skeletal muscle, increased uptake of chylomicron [3H] retinoid by rat skeletal muscle. Using [3H]retinyl palmitate and its non-hydrolyzable analog retinyl [14C]hexadecyl ether incorporated into Intralipid emulsions, the importance of retinyl ester hydrolysis in this process was assessed. We observed that 3H label was taken up to a greater extent than 14C label by rat skeletal muscle, suggesting that retinoid uptake requires hydrolysis. In summary, for each of our experiments, the level of lipoprotein lipase expression in skeletal muscle, heart, and/or adipose tissue influenced the amount of [3H]retinoid taken up from chylomicrons and/ or their remnants. —van Bennekum, A. M., Y. Kako, P. H. Weinstock, E. H. Harrison, R. J. Deckelbaum, I. J. Goldberg, and W. S. Blaner. Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester. J. Lipid Res. 1999. 40: 565–574.
Highlights
25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues
To assess whether modulation of the level of expression of lipoprotein lipase (LpL) in tissues can alter the uptake of retinoid from chylomicrons, we studied the clearance of rat mesenteric chylomicrons containing [3H]retinyl ester in three different strains of mice: wild type (WT), LpL-deficient mice that overexpress human LpL in muscle only (MCK/LpL0), and wild type mice overexpressing human LpL in muscle (MCK/LpL2)
In order better to understand whether retinyl ester hydrolysis is a prerequisite for LpL-mediated clearance of retinoid from chylomicrons and their remnants, we investigated the uptake of emulsion particles that had been doubly labeled with [3H]retinyl palmitate and its nonhydrolyzable ether analog retinyl [14C]hexadecyl ether
Summary
25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues. The tissue sites of uptake of 3H label by wild type mice and LpL-null mice overexpressing human LpL in muscle indicate that LpL expression does influence accumulation of chylomicron retinoid. Skeletal muscle from mice overexpressing human LpL accumulated 1.7- to 2.4-fold more 3H label than wild type. Heart tissue from mice overexpresssing human LpL, but lacking mouse LpL, accumulated less than half of the 3H-label taken up by wild type heart. Two factors that increase LpL activity in skeletal muscle, increased uptake of chylomicron [3H] retinoid by rat skeletal muscle. For each of our experiments, the level of lipoprotein lipase expression in skeletal muscle, heart, and/or adipose tissue influenced the amount of [3H]retinoid taken up from chylomicrons and/ or their remnants.—van Bennekum, A. Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester.
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