Vitamin A Supplementation Increases the Uptake of Chylomicron Retinyl Esters into the Brain of Neonatal Rats Raised under Vitamin A–Marginal Conditions

Hodges, Joanna; Tan, Libo; Green, Michael H.; Ross, A. Catharine

doi:10.3945/jn.116.233692

Cited by 13 publications

(22 citation statements)

References 42 publications

(51 reference statements)

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“…Rats were housed and fed according to a protocol reported previously (12,16). Briefly, eleven pregnant Sprague-Dawley (Charles River Laboratories) rats were fed a VA-marginal (0.35 mg retinol equivalents/kg) AIN-93G purified diet (Research Diets) (17) to render their pups into a state similar to that of low-birth-weight infants in regions with a high prevalence of VA deficiency.…”

Section: Rats and Dietmentioning

confidence: 99%

“…The VA supplement consisted of all-trans retinyl palmitate (Sigma-Aldrich) in the amount of 50,000 IU/2.5 kg of body weight, as given to human infants (19), or 200 IU for a neonatal rat weighing 10 g. The proportion of labeled-to-unlabeled retinol in the supplemented dose was w0.05%. Doses were prepared and administered by using a method described in prior reports (12,16).…”

Section: Dose Administrationmentioning

confidence: 99%

“…Tracer concentration and retinol mass were measured in plasma and tissue lipid extracts obtained by using a procedure described earlier (16,20). Radioactivity analysis was performed with the use of an LS 6500 liquid-scintillation counting system (Beckman Coulter) with each sample counted to a 1% error.…”

Section: Tracer and Retinol Mass Analysismentioning

confidence: 99%

“…Because the uptake of retinol from plasma was assumed to be unidirectional, the loss of retinol from organs (referred to as turnover) included both the amount released back to plasma and the amount metabolized locally. Correcting the organ tracer data for the tracer present in organ's residual plasma was previously found not to affect the values of kinetic parameters (16); therefore, all organs were modeled by using the uncorrected data.…”

Section: Kinetic Analysismentioning

confidence: 99%

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

Hodges

Tan

Green

et al. 2017

The American Journal of Clinical Nutrition

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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, nonhepatic 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 mCi of [ 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 w2 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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Section: Rats and Dietmentioning

confidence: 99%

Section: Dose Administrationmentioning

confidence: 99%

Section: Tracer and Retinol Mass Analysismentioning

confidence: 99%

Section: Kinetic Analysismentioning

confidence: 99%

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

Hodges

Tan

Green

et al. 2017

The American Journal of Clinical Nutrition

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“…In this secondary analysis, we combined data from the VA and VARA studies ( 7 , 11 , 12 ) and used the model-based compartmental analysis to compare the concentration and kinetics of retinol in several organs of neonatal rats dosed with either VA or VARA or placebo in the amount equivalent to that which has been given to human infants ( 13 ). Our results build on previous knowledge of the neonatal VA metabolism and may help inform the most effective treatment of VA deficiency in neonates by comparing the effect of 2 different supplement forms on retinol tissue uptake and distribution.…”

Section: Introductionmentioning

confidence: 99%

Vitamin A and Retinoic Acid Combined Have a More Potent Effect Compared with Vitamin A Alone on the Uptake of Retinol into Extrahepatic Tissues of Neonatal Rats Raised under Vitamin A–Marginal Conditions

Hodges

Tan

Green

et al. 2017

Current Developments in Nutrition

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Background Vitamin A (VA, retinol) supplementation is widely used to reduce child mortality in low-income countries. However, existing research suggests that supplementation with VA alone may not be optimal for infants. Objective We compared the effect of VA vs. VA combined with retinoic acid (VARA) on retinol uptake and turnover in organs of neonatal rats raised under VA-marginal conditions. Methods Secondary analysis was conducted on data obtained from two prior kinetic studies of Sprague-Dawley neonatal rats nursed by mothers fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal d 4, pups had been treated with a single dose of VA (6 μg/g; n = 52; VA study), VA + 10% retinoic acid (6 μg/g; n = 42; VARA study) or placebo (canola oil; n = 94; both studies), all containing ~2 μCi of [3H]retinol as the tracer for VA. Total retinol concentrations and tracer levels had been measured in plasma and tissues from 1 h to 14 d after dosing. Control group data from both studies were merged prior to analysis. Kinetic parameters were re-estimated and compared statistically. Results VARA supplementation administered to neonatal rats within a few days after birth resulted in a lower turnover of retinol in the lungs, kidneys, and carcass and less frequent recycling of retinol between plasma and organs (100 vs. 288 times in VARA- vs. VA-treated group). Although the VA supplementation resulted in a higher concentration of retinol in the liver, VARA supplementation led to a higher uptake of postprandial retinyl esters into the lungs, intestines, and carcass. Conclusions Given the relatively higher retinol uptake into several extrahepatic organs of neonates dosed orally with VARA, this form of supplementation may serve as a targeted treatment of low VA levels in the extrahepatic organs that continue to develop postnatally.

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Normalization of hippocampal retinoic acid level corrects age-related memory deficits in rats

Dumetz

Buré

Alfos

et al. 2020

Neurobiology of Aging

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Vitamin A Supplementation Increases the Uptake of Chylomicron Retinyl Esters into the Brain of Neonatal Rats Raised under Vitamin A–Marginal Conditions

Abstract: Postprandial chylomicrons may be a primary mechanism for delivering a recently ingested large dose of VA to the brain of neonatal rats raised under VA-marginal conditions.

Cited by 13 publications

References 42 publications

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

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

Vitamin A and Retinoic Acid Combined Have a More Potent Effect Compared with Vitamin A Alone on the Uptake of Retinol into Extrahepatic Tissues of Neonatal Rats Raised under Vitamin A–Marginal Conditions

Normalization of hippocampal retinoic acid level corrects age-related memory deficits in rats

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