Vitamin A Supplementation Transiently Increases Retinol Concentrations in Extrahepatic Organs of Neonatal Rats Raised under Vitamin A–Marginal Conditions 1–3

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 m g 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 m mol/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%.Whiteadiposetissue(WAT),whichwasnearlyabsentbeforepostnatalday12,containedonly ; 1%.InVA-supplemented neonates,themeantotalretinolconcentrationsinallorgansweresignificantlygreaterthanincontrolpups. However, thisincrease 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. J Nutr 2016;146:1953–60.

[1]  A. Ross,et al.  Vitamin A kinetics in neonatal rats vs. adult rats: comparisons from model-based compartmental analysis. , 2015, The Journal of nutrition.

[2]  G. Duester,et al.  Mechanisms of retinoic acid signalling and its roles in organ and limb development , 2015, Nature Reviews Molecular Cell Biology.

[3]  A. Ross,et al.  Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats[S] , 2014, Journal of Lipid Research.

[4]  S. Tanumihardjo,et al.  Oral doses of α-retinyl ester track chylomicron uptake and distribution of vitamin A in a male piglet model for newborn infants. , 2014, The Journal of nutrition.

[5]  P. Wierzbicki,et al.  Short-term calorie restriction and refeeding differently affect lipogenic enzymes in major white adipose tissue depots of young and old rats. , 2014, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[6]  J. Gregory,et al.  1 Vitamin A: Nutritional Aspects of Retinoids and Carotenoids , 2013 .

[7]  P. Sengupta.  The Laboratory Rat: Relating Its Age With Human's , 2013, International journal of preventive medicine.

[8]  Z. Bhutta,et al.  Impact of vitamin A supplementation on infant and childhood mortality , 2011, BMC public health.

[9]  W. Blaner,et al.  Vitamin A Metabolism: An Update , 2011, Nutrients.

[10]  H. Senoo,et al.  Hepatic stellate cell (vitamin A‐storing cell) and its relative – past, present and future , 2010, Cell biology international.

[11]  H. Sachdev,et al.  Neonatal vitamin A supplementation for prevention of mortality and morbidity in infancy: systematic review of randomised controlled trials , 2009, BMJ : British Medical Journal.

[12]  A. Sommer,et al.  Vitamin a deficiency and clinical disease: an historical overview. , 2008, The Journal of nutrition.

[13]  S. Tanumihardjo,et al.  Vitamin A concentrations in piglet extrahepatic tissues respond differently ten days after vitamin A treatment. , 2008, The Journal of nutrition.

[14]  R. Russell,et al.  Kinetic analysis shows that vitamin A disposal rate in humans is positively correlated with vitamin A stores. , 2008, The Journal of nutrition.

[15]  Robert E Black,et al.  What works? Interventions for maternal and child undernutrition and survival , 2008, The Lancet.

[16]  Ipcs,et al.  Principles for evaluating health risks in children associated with exposure to chemicals , 2006 .

[17]  N. Ambalavanan,et al.  Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats Published, JLR Papers in Press, May 9, 2006. , 2006, Journal of Lipid Research.

[18]  P. Nilsson-ehle,et al.  Concentrations of retinoids in early pregnancy and in newborns and their mothers. , 2005, The American journal of clinical nutrition.

[19]  P. Reczek,et al.  Lung retinol storing cells synthesize and secrete retinoic acid, an inducer of alveolus formation. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[20]  A. Ross,et al.  Retinoid production and catabolism: role of diet in regulating retinol esterification and retinoic Acid oxidation. , 2003, The Journal of nutrition.

[21]  D. Liberato,et al.  Plasma kinetics of vitamin A in humans after a single oral dose of [8,9,19-13C]retinyl palmitate. , 1996, Journal of lipid research.

[22]  M. Pfahl,et al.  Regulation of metabolism by retinoic acid and its nuclear receptors. , 1996, Annual review of nutrition.

[23]  C. Bates.  Vitamin A , 1995, The Lancet.

[24]  M. Green,et al.  Vitamin A intake and status influence retinol balance, utilization and dynamics in rats. , 1994, The Journal of nutrition.

[25]  P. G. Reeves,et al.  AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. , 1993, The Journal of nutrition.

[26]  F. Mosteller,et al.  Vitamin A supplementation and child mortality. A meta-analysis. , 1993, JAMA.

[27]  M. Allan,et al.  Retinoids and retinoid-binding protein expression in rat adipocytes. , 1992, The Journal of biological chemistry.

[28]  A. Costello.  Vitamin A supplementation , 1991, The Lancet.

[29]  R Ross,et al.  Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats. , 1991, Journal of applied physiology.

[30]  B. Underwood.  Methods for assessment of vitamin A status. , 1990, The Journal of nutrition.

[31]  M. Green,et al.  Retinol metabolism in rats with low vitamin A status: a compartmental model. , 1990, Journal of lipid research.

[32]  A. Sommer,et al.  VITAMIN A SUPPLEMENTATION AND CHILD MORTALITY , 1986, The Lancet.

[33]  M. Green,et al.  A multicompartmental model of vitamin A kinetics in rats with marginal liver vitamin A stores. , 1985, Journal of lipid research.

[34]  D. Roop,et al.  Vitamin A: a key nutrient for the maintenance of epithelial differentiation. , 1985, Acta vitaminologica et enzymologica.

[35]  J. Olson,et al.  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. , 1983, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[36]  A. Masters,et al.  Red cell and plasma volume development in newborn rats measured with double label. , 1972, The American journal of physiology.