Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/1999
Publication Date: N/A
Interpretive Summary: After a meal, the vitamin A contained in it is delivered to the body's tissues from the blood in a complex with other dietary fats. While most of the meal's vitamin A is delivered to the liver, as much as 25% is taken up by other extrahepatic (non-liver) tissues including skeletal muscle, heart and adipose (fat) tissue. In these studies we show that the level of a particular enzyme involved in fat metabolism (called lipoprotein lipase or LPL) in these tissues regulated the amount of vitamin A taken up by those tissues. The level of LPL in these non-liver tissues of mice was manipulated by nutritional and genetic engineering techniques. This research will benefit scientists studying the metabolism of vitamin A and will then help to understand the whole body economy of this essential vitamin.
Technical Abstract: As much as 25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues including, skeletal muscle, heart, adipose tissue and kidney but little is known about the factors. We hypothesized that lipoprotein lipase (LpL) plays a role in the clearance of dietary vitamin A by extrahepatic tissues. To test this, [3H]retinylester-containing rat chylomicrons were injected intravenously into induced mutant mice and nutritionally manipulated rats and the plasma clearance and tissue sites of uptake of the 3H-label was assessed. Data obtained from wild type mice, LpL-null mice which over express human LpL in muscle and wild type mice over expressing human LpL in muscle, indicate that the level of LpL expression influences extrahepatic tissue accumulation of 3H-label from chylomicrons labeled with [3H]retinyl ester. Skeletal muscle from mice over expressing LpL reproducibly accumulated 1.7 to 2.4-fold more [3H]retinyl than did tissue from wild type mice. The heart of LpL-null mice over expressing human LpL in skeletal muscle, but lacking LpL in heart, accumulated less than one-half of the 3H-label taken up by wild type hearts. The effects of fasting and feeding and heparin injection, factors which markedly influence LpL activity in skeletal muscle and adipose tissue, on the plasma clearance and tissue uptake of chylomicron [3H]retinoid was assessed in rats. We observed marked differences in both the rate of retinoid clearance from the circulation and in the levels of 3H-label accumulated by skeletal muscle and adipose tissue. Overall, these data are consistent with the hypothesis that the level of extrahepatic tissue LpL expression influences tissue retinoid accumulation from chylomicrons and/or their remnants.