Vitamin A Kinetics in Neonatal Rats vs. Adult Rats: Comparisons from Model-Based Compartmental Analysis,

Abstract

A critical role for vitamin A (VA) in development is well established, but still relatively little is known about whole-body VA metabolism in early postnatal life. Recently, methods of mathematical modeling have begun to shed light on retinol kinetics in the postnatal growth period and on the effect of retinoid supplementation on retinol kinetics. Comparison of kinetic parameters from tracer studies in neonatal rats with those previously determined in models of VA metabolism in the adult suggests both similarities and differences in the relative transfer rates of plasma retinol to extrahepatic tissues, resulting in similarities and differences in kinetic parameters and inferences about physiologic processes. Similarities between neonatal and adult models include the capacity for efficient digestion and absorption of VA; characteristics of a high-response system; extensive retinol recycling among liver, plasma, and extrahepatic tissues; and comparable VA disposal rates. Differences between neonatal and adult models include that, in neonates, retinol turnover is faster and retinol recycling is much more extensive; there is a greater role for extrahepatic tissues in the uptake of chylomicron VA; and the intestine plays an important role in chylomicron VA uptake, especially in neonatal rats treated with a supplement containing VA. In summary, retinol kinetic modeling in the neonatal rat has provided a first view of whole-body VA metabolism in this age group and suggests that VA kinetics in neonatal rats differs in many ways from that in adults, perhaps reflecting an adaption to the lower VA concentration found in neonates compared with adults.

Vitamin A supplementation redirects the flow of retinyl esters from peripheral to central organs of neonatal rats raised under vitamin A–marginal conditions

“…The preliminary findings of these studies indicate that, compared with adult rats in a similar VA status, the extrahepatic tissues in neonates store relatively little VA (13% compared with 44% in adult rats) (12), despite a higher proportion of retinyl esters (REs) being acquired by these tissues (40% compared with 25%) (13). VA supplementation increased the concentration of retinol in most extrahepatic organs, but only transiently (for w1 d) (12), suggesting that the extrahepatic tissues in neonates may have a limited retinol storage capacity.…”

Plasma Retinol Kinetics and β-Carotene Bioefficacy Are Quantified by Model-Based Compartmental Analysis in Healthy Young Adults with Low Vitamin A Stores

“…Model-based compartmental analysis [specifically, the Simulation, Analysis and Modeling software (WinSAAM; http://www.WinSAAM.org ) ( 1 )] has been productively used to describe and quantitate retinol kinetics in rats over the past 35 y [see reference 2 for a review as well as Tan et al ( 3 )]. This approach has generated unique and important insights into whole-body vitamin A metabolism, including the fact that there is extensive recycling of retinol among plasma and tissues before irreversible utilization.…”

Vitamin A Supplementation Transiently Increases Retinol Concentrations in Extrahepatic Organs of Neonatal Rats Raised under Vitamin A–Marginal Conditions

“…Specifically, we aimed to examine the concentration and mass of retinol in tissues that have been relatively unexplored from the perspective of VA metabolism, such as brain, skin, white adipose tissue (WAT), and brown adipose tissue (BAT). Previous studies have shown that neonates store a greater proportion (51% compared with 44%) of the whole-body VA mass than adult rats in tissues other than the liver, which is the main VA storage organ in VA-sufficient rodents (13). Moreover, a single dose of VA admixed with retinoic acid (VARA) stimulated the uptake of VA by extrahepatic tissues, especially the carcass and intestine, which together acquired ;75% of the recently ingested VA (14).…”