Acidic retinoids in small amounts promote retinyl ester formation in neonatal lung, with transient increases in retinoid homeostatic gene expression

Lili Wu, Reza Zolfaghari, A. Catharine Ross

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3 Scopus citations

Abstract

Background: Mixing a small proportion, 10%, of retinoic acid (RA) into an oral dose of vitamin A (VA) has been shown to markedly increase retinol uptake and retinyl ester (RE) formation in the neonatal lung, as compared to VA given alone. Concomitantly, several retinoid homeostatic genes, lecithin:retinol acyltransferase (LRAT), RA-4-hydroxylase (CYP26B1), and stimulated by retinoic acid gene-6 (STRA6) were upregulated. However, whether multiple doses may act accumulatively and whether less than 10% RA can be used has not been determined. Methods. Neonatal rats were treated once on postnatal day (PD) 4 or PD14 with VA alone or VA combined with 10% RA (VARA10%) or a stable analog, Am580 (VAAm10%), or they were treated with multiple doses on PD4, 7, 11, and 14. Results: RE increased cumulatively with multiple dosing. However, LRAT, CYP26B1 and STRA6 mRNA levels were similar for single and multiple treatments, indicating a transient noncumulative impact on gene expression. Lung RE was elevated with as little as 0.5% RA (P < 0.05) in a single dosing study. Whereas all concentrations of VARA elevated lung RE in single dosing studies, only 10% RA increased lung RE after multiple dosing, suggesting an attenuation of RA action with repeated dosing. In contrast, VAAm10%, 2%, and 1% all significantly increased lung RE after multiple doses (P < 0.05), while also increasing the expression of LRAT and CYP26B1. Conclusions: These results indicate that the neonatal lung is very sensitive to acidic retinoid exposure and suggest that a VA combined with a very small fraction of acidic retinoid could be effective in increasing the lung's storage pool of VA.

Original languageEnglish (US)
Article number72
JournalNutrition and Metabolism
Volume10
Issue number1
DOIs
StatePublished - Dec 19 2013

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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