Chylomicron Margination, Lipolysis, and Vitamin A Uptake in the Lactating Rat Mammary Gland: Implications for Milk Retinoid Content

Abstract

We have reported previously that the concentration of vitamin A (VA) in the milk of lactating rats varies with dietary VA intake, even when plasma retinol concentration is unaffected. In the current study, we investigated the role of lipolysis in the uptake of chylomicron (CM) VA into mammary tissue of lactating rats and estimated the proportion of CM-VA that is associated with the mammary gland during CM clearance. Chylomicrons containing [3H]VA, mainly as retinyl esters, were prepared in donor rats and administered intravenously to lactating recipient rats. Chylomicron VA rapidly disappeared from plasma and appeared in mammary tissue (maximum within 2–3 mins), followed by a decline. Concomitantly, uptake by liver increased continuously, reaching a plateau within 20–30 mins. Active lipolysis in mammary tissue was necessary for rapid VA uptake, as significantly less CM-VA was recovered in mammary tissue of postlactating rats than of lactating rats, after heparin treatment in lactating rats, or after injection of preformed CM remnants in lactating rats. [3H]Vitamin A uptake by mammary tissue increased linearly with CM-VA dose over a 150-fold dose range (R2 = 0.972, P = 0.0001), suggesting a high capacity for uptake and apparent first-order assimilation of CM-VA during CM remnant formation in situ. Model-based compartmental analysis using WinSAAM predicted that ~42% of CM-VA marginated, that is, were temporarily removed, from plasma to the mammary glands during lipolysis and that a total of 3.8% of CM-VA was transferred to mammary tissue. The model-predicted t1/2 for CM remnants was 3.04 mins. The metabolism of CM-VA in the lactating mammary gland, in proportion to VA absorption and CM-VA contents, may explain how milk VA concentration varies even when plasma retinol levels are unchanged. The mechanism of CM margination and mammary gland uptake described here for VA may be similar for other lipophilic substances.