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Journal of Lipid Research, Vol. 47, 1844-1851, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats

A. Catharine Ross^1,*,, Namasivayam Ambalavanan, Reza Zolfaghari^* and Nan-qian Li^*

^* Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802
Huck Institute for Life Sciences, Pennsylvania State University, University Park, PA 16802
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35249

Published, JLR Papers in Press, May 9, 2006.

¹ To whom correspondence should be addressed. e-mail: acr6{at}psu.edu

Vitamin A (VA) is stored in tissues predominantly as retinyl esters (REs), which provide substrate for the production of bioactive retinoids. Retinoic acid (RA), a principal metabolite, has been shown to induce postnatal lung development. To better understand lung RE storage, we compared VA (given as retinyl palmitate), RA, and a nutrient-metabolite combination, VARA, given orally on postnatal days 5–7, for their ability to increase lung RE in neonatal rats. VARA increased lung RE significantly [14, 2.4, 2.1, and <1 nmol/g for VARA, VA, RA, and control (C), respectively; P < 0.001]; the increase by VARA was more than additive compared with the effects of VA and RA alone. Lung histology and morphometry were unchanged. In a 6 h metabolic study, providing [³H]retinol with VARA, compared with VA or C, increased the uptake of newly absorbed ³H by 3-fold, indicating that VARA stimulated the uptake of [³H]retinol and its retention as [³H]RE in neonatal lungs. After cessation of VARA, lung RE remained increased for 9 d afterward, through the period of alveolar development. In conclusion, VARA, a 10:1 nutrient-metabolite combination, increased lung RE significantly compared with VA alone and could be a promising therapeutic option for enhancing the delivery of VA to the lungs.

Supplementary key words lung retinyl ester storage • retinol esterification • liver retinyl ester • newly absorbed retinol • neonatal vitamin A status

Abbreviations: RA, retinoic acid; RE, retinyl ester; VA, vitamin A

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