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

Overview

Journal J Nutr

Publisher Elsevier

Specialty Nutritional Sciences

Date 2016 Aug 19

PMID 27534819

Citations 6

Authors

Joanna K Hodges

Libo Tan

Michael H Green

A Catharine Ross

Affiliations

Soon will be listed here.

Abstract

Background: Vitamin A (VA; retinol) supplementation is recommended for children aged >6 mo in countries with high rates of malnutrition, but the distribution and retention of VA in body tissues have not been extensively explored.

Objective: We sought to determine the distribution and retention of VA in tissues of neonatal rats raised under VA-marginal conditions.

Methods: Sprague-Dawley neonatal rats (n = 104; 63 males) nursed by mothers fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet) were randomized and treated on postnatal day 4 with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil as control. Pups (n = 4/group) were killed at 13 time points from 30 min to 24 d after dose administration. The total retinol concentration and mass were determined in all collected organs.

Results: In the control group, plasma VA was marginal (0.8 μmol/L), whereas liver VA was deficient (<70 nmol/g). Nonetheless, the liver contained most (∼76%) of the total VA mass in the body, whereas extrahepatic nondigestive organs together contained ∼13%. White adipose tissue (WAT), which was nearly absent before postnatal day 12, contained only ∼1%. In VA-supplemented neonates, the mean total retinol concentrations in all organs were significantly greater than in control pups. However, this increase lasted for only ∼1 d in most extrahepatic tissues, with the exception of WAT, in which it lasted 18 d.

Conclusions: Extrahepatic organs in neonatal rats raised under VA-marginal conditions store relatively little VA, and the scarcity of adipose tissue may predispose neonates to a low-VA status. The effect of VA supplementation on VA content in most extrahepatic organs is transient. A more frequent supplementation along with other nutritional interventions may be necessary for maintaining a steady supply of retinol to the rapidly developing extrahepatic organs.

Citing Articles

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Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review.

Gannon B, Rogers L, Tanumihardjo S Adv Nutr. 2020; 12(3):942-958.

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Retinoic Acid Mediated Clearance of in Vitamin A Deficient Mice Requires CD11b+ and T Cells.

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Vitamin A and retinoic acid combined have a more potent effect compared to vitamin A alone on the uptake of retinol into extrahepatic tissues of neonatal rats raised under vitamin A-marginal conditions.

Hodges J, Tan L, Green M, Ross A Curr Dev Nutr. 2018; 1(12).

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Single High-Dose Vitamin A Supplementation to Neonatal Piglets Results in a Transient Dose Response in Extrahepatic Organs and Sustained Increases in Liver Stores.

Gannon B, Davis C, Nair N, Grahn M, Tanumihardjo S J Nutr. 2017; 147(5):798-806.

PMID: 28381532 PMC: 6584120. DOI: 10.3945/jn.117.247577.

References

Bhutta Z, Ahmed T, Black R, Cousens S, Dewey K, Giugliani E . What works? Interventions for maternal and child undernutrition and survival. Lancet. 2008; 371(9610):417-40. DOI: 10.1016/S0140-6736(07)61693-6. View

Riabroy N, Tanumihardjo S . Oral doses of α-retinyl ester track chylomicron uptake and distribution of vitamin A in a male piglet model for newborn infants. J Nutr. 2014; 144(8):1188-95. DOI: 10.3945/jn.114.191668. View

Ross A, Ambalavanan N, Zolfaghari R, Li N . Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats. J Lipid Res. 2006; 47(8):1844-51. DOI: 10.1194/jlr.M600061-JLR200. View

Wronska A, Sledzinski T, Goyke E, Lawniczak A, Wierzbicki P, Kmiec Z . Short-term calorie restriction and refeeding differently affect lipogenic enzymes in major white adipose tissue depots of young and old rats. J Physiol Pharmacol. 2014; 65(1):117-26. View

Ross A . Separation and quantitation of retinyl esters and retinol by high-performance liquid chromatography. Methods Enzymol. 1986; 123:68-74. DOI: 10.1016/s0076-6879(86)23010-4. View

Tan L, Green M, Ross A . Vitamin A kinetics in neonatal rats vs. adult rats: comparisons from model-based compartmental analysis. J Nutr. 2014; 145(3):403-10. PMC: 4336526. DOI: 10.3945/jn.114.204065. View

Pfahl M, Chytil F . Regulation of metabolism by retinoic acid and its nuclear receptors. Annu Rev Nutr. 1996; 16:257-83. DOI: 10.1146/annurev.nu.16.070196.001353. View

Sommer A . Vitamin a deficiency and clinical disease: an historical overview. J Nutr. 2008; 138(10):1835-9. DOI: 10.1093/jn/138.10.1835. View

Underwood B . Methods for assessment of vitamin A status. J Nutr. 1990; 120(Suppl 11):1459-63. DOI: 10.1093/jn/120.suppl_11.1459. View

10.

Dahro M, Gunning D, Olson J . Variations in liver concentrations of iron and vitamin A as a function of age in young American children dying of the sudden infant death syndrome as well as of other causes. Int J Vitam Nutr Res. 1983; 53(1):13-8. View

11.

Sun T, Surles R, Tanumihardjo S . Vitamin A concentrations in piglet extrahepatic tissues respond differently ten days after vitamin A treatment. J Nutr. 2008; 138(6):1101-6. PMC: 2678969. DOI: 10.1093/jn/138.6.1101. View

12.

Imdad A, Yakoob M, Sudfeld C, Haider B, Black R, Bhutta Z . Impact of vitamin A supplementation on infant and childhood mortality. BMC Public Health. 2011; 11 Suppl 3:S20. PMC: 3231894. DOI: 10.1186/1471-2458-11-S3-S20. View

13.

Berggren Soderlund M, Fex G, Nilsson-Ehle P . Concentrations of retinoids in early pregnancy and in newborns and their mothers. Am J Clin Nutr. 2005; 81(3):633-6. DOI: 10.1093/ajcn/81.3.633. View

14.

Cunningham T, Duester G . Mechanisms of retinoic acid signalling and its roles in organ and limb development. Nat Rev Mol Cell Biol. 2015; 16(2):110-23. PMC: 4636111. DOI: 10.1038/nrm3932. View

15.

DAmbrosio D, Clugston R, Blaner W . Vitamin A metabolism: an update. Nutrients. 2011; 3(1):63-103. PMC: 3042718. DOI: 10.3390/nu3010063. View

16.

Senoo H, Yoshikawa K, Morii M, Miura M, Imai K, Mezaki Y . Hepatic stellate cell (vitamin A-storing cell) and its relative--past, present and future. Cell Biol Int. 2010; 34(12):1247-72. DOI: 10.1042/CBI20100321. View

17.

Biesalski H, Nohr D . Importance of vitamin-A for lung function and development. Mol Aspects Med. 2003; 24(6):431-40. DOI: 10.1016/s0098-2997(03)00039-6. View

18.

Green M, Green J . Vitamin A intake and status influence retinol balance, utilization and dynamics in rats. J Nutr. 1994; 124(12):2477-85. DOI: 10.1093/jn/124.12.477. View

19.

Green M, Uhl L, Green J . A multicompartmental model of vitamin A kinetics in rats with marginal liver vitamin A stores. J Lipid Res. 1985; 26(7):806-18. View

20.

Ross A . Retinoid production and catabolism: role of diet in regulating retinol esterification and retinoic Acid oxidation. J Nutr. 2003; 133(1):291S-296S. DOI: 10.1093/jn/133.1.291S. View