Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester

Approximately 25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues. Little is known about physiologic factors importan t to this uptake. We hypothesized that lipoprotein lipase (LpL) contributes to extrahepatic clearance of chylomicron vitamin A. To investigate this, [ H-3]retinyl ester-containing rat mesenteric chylomicrons were injected intr avenously into induced mutant mice and nutritionally manipulated rats. The tissue sites of uptake of H-3 label by wild type mice and LpL-null mice ove rexpressing human LpL in muscle indicate that LpL expression does influence accumulation of chylomicron retinoid, Skeletal muscle from mice overexpres sing human LPL accumulated 1.7- to 2.4-fold more SH label than wild type, M oreover, heart tissue from mice overexpresssing human LpL, but lacking mous e LpL, accumulated less than half of the H-3-label taken up by wild type he art. Fasting and heparin injection, two factors that increase LpL activity in skeletal muscle, increased uptake of chylomicron [H-3] retinoid by rat s keletal muscle. Using [H-3]retinyl palmitate and its non-hydrolyzable analo g retinyl [C-14]hexadecyl ether incorporated into Intralipid emulsions, the importance of retinyl ester hydrolysis in this process was assessed. We ob served that H-3 label was taken up to a greater extent than C-14 label by rat skeletal muscle, suggesting that retinoid up take requires hydrolysis.j lr 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.