4.7 Article

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

Journal

AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 105, Issue 5, Pages 1110-1121

Publisher

ELSEVIER SCIENCE INC
DOI: 10.3945/ajcn.116.149039

Keywords

chylomicron; extrahepatic; growth and development; mathematical modeling; neonate; retinyl esters; vitamin A deficiency; vitamin A metabolism; vitamin A supplementation

Funding

  1. Pennsylvania State University Graduate Program in Nutrition
  2. Dorothy Foehr Huck Endowment
  3. NIH [HD-066982]

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Background: Vitamin A (VA; retinol) supplementation is used to reduce child mortality in countries with high rates of malnutrition. Existing research suggests that neonates (< 1 mo old) may have a limited capacity to store VA in organs other than the liver; however, knowledge about VA distribution and kinetics in individual, non-hepatic organs is limited. Objective: We examined retinol uptake and turnover in nonhepatic organs, including skin, brain, and adipose tissue, in neonatal rats without and after VA supplementation. Design: Sprague-Dawley neonatal rats (n = 104) were nursed by mothers fed a VA-marginal diet (0.35 mg retinol/kg diet) and treated on postnatal day 4 with an oral dose of either VA (6 mg retinyl palmitate/g body weight) or canola oil (control), both containing 1.8 mu Ci of [H-3] retinol. Subsequently, pups (n = 4 . group(-1) . time(-1)) were killed at 13 different times from 30 min to 24 d after dosing. The fractional and absolute transfer of chylomicron retinyl esters (CM-REs), retinol bound to retinol-binding protein (RBP-ROH), and total retinol were estimated in WinSAAM software. Results: VA supplementation redirected the flow of CM-REs from peripheral to central organs and accumulated mainly in the liver. The RBP-ROH released from the liver was acquired mainly by the peripheral tissues but not retained efficiently, causing repeated recycling of retinol between plasma and tissues (541 compared with 5 times in the supplemented group and control group, respectively) and its rapid turnover in all organs, except the brain and white adipose tissue. Retinol stores in the liver lasted for similar to 2 wk before being gradually transferred to other organs. Conclusions: VA supplementation administered in a single high dose during the first month after birth is readily acquired but not retained efficiently in peripheral tissues of neonatal rats, suggesting that a more frequent, lower-dose supplementation may be necessary to maintain steady VA concentrations in rapidly developing neonatal tissues.

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