what happens to an animal raised on retinoic acid as its only source of vitamin a?
J Nutr. 2022 October; 146(10): 1953–1960.
Vitamin A Supplementation Transiently Increases Retinol Concentrations in Extrahepatic Organs of Neonatal Rats Raised nether Vitamin A–Marginal Conditions1, 2, 3
Received 2022 April nineteen; Revised 2022 May 19; Accepted 2022 Jul 11.
Abstract
Groundwork: 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 memory of VA in tissues of neonatal rats raised under VA-marginal atmospheric condition.
Methods: Sprague-Dawley neonatal rats (northward = 104; 63 males) nursed past 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 torso weight) or canola oil as control. Pups (due north = 4/group) were killed at 13 fourth dimension points from xxx min to 24 d later on dose assistants. 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/chiliad). Notwithstanding, the liver contained nearly (∼76%) of the full VA mass in the body, whereas extrahepatic nondigestive organs together contained ∼13%. White adipose tissue (WAT), which was nearly absent before postnatal solar day 12, independent merely ∼i%. In VA-supplemented neonates, the hateful total retinol concentrations in all organs were significantly greater than in control pups. Notwithstanding, this increase lasted for but ∼1 d in most extrahepatic tissues, with the exception of WAT, in which it lasted eighteen d.
Conclusions: Extrahepatic organs in neonatal rats raised under VA-marginal conditions shop relatively niggling VA, and the scarcity of adipose tissue may predispose neonates to a depression-VA status. The effect of VA supplementation on VA content in most extrahepatic organs is transient. A more than frequent supplementation along with other nutritional interventions may be necessary for maintaining a steady supply of retinol to the rapidly developing extrahepatic organs.
Keywords: adipose, brain, extrahepatic, neonate, rat, retinol, skin, tissue distribution, vitamin A supplementation
Introduction
Vitamin A (VA5; retinol) is essential for the proliferation and differentiation of many dissimilar cell types and thus the development of the entire organism (1–three). Given the rapid growth that occurs during the neonatal flow, information technology is reasonable to postulate that neonates take an increased need for VA. Studies accept shown, all the same, that even salubrious infants are built-in with low concentrations of VA in plasma and in the liver (<0.7 μM and < 10 μg/g, respectively), concentrations that would indicate deficiency if observed in older age groups (4, 5).
In addition to its role in cell differentiation, VA is also essential for allowed response, and the problem of high infant mortality caused by infections in countries with high rates of VA deficiency has been recognized for many decades (half-dozen). In view of this problem, the WHO has initiated numerous clinical trials, several of which are yet ongoing, to examine the outcome of large-dose VA supplementation (l,000 IU/ii.5 kg body weight) on babe survival (7). A meta-analysis of randomized clinical trials in which VA was given to children aged 6–59 mo revealed a 23–34% reduction in child mortality (8–10). On the other hand, VA supplementation administered to newborns within the beginning few days of life did non significantly touch on bloodshed outcomes in infants aged <vi mo, despite several studies conducted in this age group (11, 12). The verbal fate of VA administered to newborns remains, to a big extent, poorly understood.
In this study, our objective was to help fill this knowledge gap past determining the distribution of VA in tissues of neonatal rats, without and later VA supplementation at a dose equivalent—later on adjusting for body weight (∼ten g)—to the dose that has been given to infants (fifty,000 IU/ii.5 kg torso weight). Specifically, nosotros aimed to examine the concentration and mass of retinol in tissues that have been relatively unexplored from the perspective of VA metabolism, such every bit brain, pare, white adipose tissue (WAT), and chocolate-brown adipose tissue (BAT). Previous studies have shown that neonates store a greater proportion (51% compared with 44%) of the whole-torso VA mass than adult rats in tissues other than the liver, which is the chief VA storage organ in VA-sufficient rodents (thirteen). Moreover, a single dose of VA admixed with retinoic acid (VARA) stimulated the uptake of VA past extrahepatic tissues, especially the carcass and intestine, which together acquired ∼75% of the recently ingested VA (fourteen). In view of these findings, we focused herein on extrahepatic tissues, subdividing the carcass—which in our previous experiment included several organs—into its components and determined the effect of VA supplementation, administered without retinoic acid, on total retinol concentration in WAT, BAT, skin, encephalon, and the remaining carcass over 24 d afterward dose administration. Considering tissues grow rapidly during the neonatal period, organ weights and retinol mass accumulation over time were besides determined. The results obtained provide a more than comprehensive view of the impact of VA supplementation on neonatal tissue VA concentrations and reveal the transient nature of the effect of supplementation on extrahepatic VA storage in neonatal rats.
Methods
Animals and nutrition.
Pregnant Sprague-Dawley rats (n = 11) were purchased from Charles River Laboratories. Upon inflow, dams were switched to a VA-marginal Ain-93G-purified nutrition (15) modified to contain 0.35 mg retinol equivalents/kg diet (Research Diets) to render pups in a VA-marginal state similar to that of low-nativity-weight infants in regions with a high prevalence of VA deficiency. All dams were housed individually at 22°C in a room with a 12-h light-and-dark bicycle and given free admission to food and water. All animal procedures were approved past the Pennsylvania State University Institutional Animal Care and Use Committee.
Dose administration.
The oral VA supplement consisted of VA in the form of all-trans-retinyl palmitate (Sigma-Aldrich) calculated to evangelize 50,000 IU/two.five kg body weight, as in human studies (7). With the utilise of the conversion factor 0.548 μg retinyl palmitate/IU, the dose was half dozen μg body weight/yard (21 nmol/grand) for neonatal rats. The full amount of VA required for supplementing all pups was mixed with canola oil in proportions such that the desired VA mass would be delivered in a dose book of 0.4 μL body weight/one thousand + one μL equally an allowance for retentiveness in the pipette tip. The oil and VA doses were stored at −20°C in foil-wrapped vials to protect the VA from photodegradation.
All dams gave nativity within 2 consecutive days to a total of 116 pups that were subsequently redistributed between xi litters to avoid any effects caused by litter-size differences. Approximately x pups from each litter were randomly assigned to the control (n = 52; 30 males) and VA-supplemented (due north = 52; 33 males) groups. On postnatal day 4, all pups were treated with an oral dose of either VA or canola oil as control. Immediately after being treated, each pup was returned to its mother and allowed to eat milk (and diet afterwards weaning) for the remainder of the report.
Tissue collection.
At 13 time points later on dose administration (0.5, 1, four, 8, and 15 h and 1, 2, 4, 8, eleven, 14, eighteen, and 22 d), 4 pups/group were removed from their cages, weighed, and killed with isoflurane or, if aged >14 d, CO2. Blood was collected from the vena cava into heparinized syringes, and the following tissues were dissected: liver, tum, intestines (modest and big intestine with the contents), lungs, kidneys with adrenals, encephalon, interscapular BAT, WAT (nerveless on and subsequently postnatal twenty-four hours 12 from the inguinal and scapular depots), and the remaining carcass. Blood and liver were also collected from dams killed on the terminal day of the study. Blood samples were centrifuged at 800 × g for fifteen min and stored at −20°C. Tissue samples were snap-frozen in liquid nitrogen and stored at −fourscore°C.
Analyses of full retinol and retinyl esters.
Total retinol mass (unesterified + esterified retinol) was adamant past ultra-performance liquid chromatography (UPLC) (Acquity UPLC Organisation; Waters) with the use of an adaptation of the previously reported method (14, 16). Briefly, plasma aliquots (5–fifty μL) and tissue homogenates (∼0.2 thousand) were incubated in 100% ethanol for 1 h for lipid extraction then saponified with the use of potassium hydroxide. Neutral lipids were partitioned into hexanes containing 0.1% butylated hydroxytoluene. The sectionalisation step was repeated ii–iii times for lipid-rich tissues (brain, pare, BAT, WAT, and carcass) to attain ≥93% extraction efficiency, as adamant in prior pilot testing for these tissues. Subsequently centrifugation, the upper-phase hexanes were removed, an internal standard (trimethylmethoxyphenyl-retinol) was added, the solvent was evaporated under nitrogen, and the remainder was reconstituted immediately in 100 μL methanol for injection onto the reversed-stage column of the Acquity UPLC System. To measure retinyl esters, the saponification stride was omitted, and the UPLC run time was extended from one to vii min. All results were corrected for the unextracted portion of lipids.
Statistical analyses.
Values were expressed every bit means ± SEMs. Group means for plasma and tissue retinol mass and concentration at individual times were compared with the use of Student's t examination with Bonferroni correction for multiple comparisons (GraphPad Prism version 5.0). Changes over time were assessed with the use of uncomplicated linear regression analysis, with time as the independent variable and retinol concentration/mass every bit the dependent variable. A significant nonzero slope (β) indicated an increment or decrease over fourth dimension. P < 0.05 was considered pregnant. To compare organs in terms of VA storage capacity, the organ retinol mass was averaged betwixt postnatal days 4 and 8, when the relative organ weights were about constant (Supplemental Table one). This period in rats corresponds to ∼1–2.5 y of historic period in humans (17). The means were then compared with the use of Wilcoxon matched-pairs signed rank exam. Plasma total volume was ∼3.v% of body weight based on previously published data (18).
Results
Animate being and relative organ growth.
Animals appeared to be healthy and grew apace (from ∼x to 80 yard) without differences acquired by VA supplementation ( Effigy 1 ). The organ:trunk weight ratio was highest for the skin (0.2 ± 0.0) and carcass (0.4 ± 0.0). During the study, the organ:body weight ratio increased for the liver, intestine, and carcass and decreased for the lungs and brain. For the skin, this ratio increased before twenty-four hours 11 of the study and declined afterward (Supplemental Tabular array 1).
Neonatal rat trunk weights betwixt postnatal days 4 and 28. Inset shows the first 24 h later dose assistants. Each point represents the mean ± SEM of 4 rats. VA, vitamin A.
Digestive organs.
The concentration of retinol in the stomach was elevated from thirty min to 1 h (P < 0.01) afterward VA supplementation and declined to the control grouping concentration thereafter ( Effigy 2A ). Total retinol mass in the stomach followed a like design (Figure 2B). In the intestine, the concentration of retinol peaked at 1 h after dose administration and remained significantly elevated for 24 h (P < 0.001) (Figure 2C). Total retinol mass in the intestine remained relatively abiding despite a ∼900% increase in organ weight during the study (Figure second, inset).
Stomach (A, B) and intestine (C, D) full (unesterified + esterified) retinol concentration and mass in command and VA-supplemented neonatal rats between postnatal days 4 and 28. Insets show the first 24 h after dose assistants (A, C) and organ weights (B, D). Each indicate represents the mean ± SEM of 4 rats. *P < 0.05. VA, vitamin A.
Plasma.
In the command group, the mean concentration of retinol in plasma (0.eight ± 0.1 μmol/50) was within the marginal status of 0.7–i μM (19). In the VA-supplemented neonates, plasma retinol concentration peaked at ane h later on dose administration (3.half dozen ± 1.vii μmol/L) and returned to baseline 15 h later ( Figure 3A ). This increment was mainly acquired by retinyl esters (Effigy 3B), which are presumably present in postprandial chylomicrons. Subsequently 15 h, the plasma retinol concentration in the VA-supplemented grouping did not differ from that in the VA-marginal command group. Total retinol mass in plasma was too no unlike, except on day 14, when there was a ∼xxx% decrease in the VA-supplemented neonates (P < 0.001). After day fourteen, the mass of retinol in plasma increased more than rapidly over time than did plasma volume (Effigy 3C, inset).
Plasma total (unesterified + esterified) retinol concentration (A), retinyl ester concentration (B), and retinol mass (C) in control and VA-supplemented neonatal rats betwixt postnatal days 4 and 28. Insets evidence the commencement 24 h subsequently dose administration (A) and plasma volume (B). Each point represents the mean ± SEM of 4 rats (A, C) or a pooled sample of 4 rats killed at 1 sampling fourth dimension (B). *P < 0.05. The dotted line represents the purlieus between adequate and marginal plasma retinol concentrations (17). VA, vitamin A.
Liver, lungs, and kidneys.
In the liver of control neonates, the mean retinol concentration (59.four ± 1.8 nmol/thousand) was scarce (<seventy nmol tissue/one thousand) (twenty) and decreased steadily over time (β = −5.9 ± 1.2; P < 0.001). VA supplementation increased the full retinol concentration by 302% from the control group value at 24 h afterwards dose administration, and the concentration remained elevated at most time points until day 11 (P < 0.001) ( Figure 4A ). Total retinol mass in the liver increased in both groups until twenty-four hours xiv and and so declined and remained steady until the cease of the study (Effigy 4B) despite continuous liver growth (Effigy 4B, inset).
Liver (A, B), lung (C, D), and kidney (E, F) total (unesterified + esterified) retinol concentration and mass, respectively, in control and VA-supplemented neonatal rats between postnatal days 4 and 28. Insets evidence the kickoff 24 h after dose administration (A, C, Eastward) and organ weights (B, D, F). Each point represents the mean ± SEM of four rats. *P < 0.05. The dotted line represents the purlieus betwixt sufficient and scarce liver retinol concentrations (18). VA, vitamin A.
In the lungs of command pups, retinol concentration increased by ∼400% from days 0 to 18 (β = 0.three ± 0.0; P < 0.001). After VA supplementation, lung retinol concentration was greater than in the command group, but only at ane h (P < 0.01) and 24 h (P < 0.001) after dose assistants. This was almost likely caused past the large variation betwixt pups inside groups. Afterward day 1, lung retinol concentration tracked similarly in both groups, with a gradual increment and then a rapid decline during the last vi d of the study (Effigy 4C). The lungs also showed a progressive aggregating of retinol relative to lung weight, which lasted until days 18 and 24 in the control and VA-supplemented neonates, respectively (Figure 4D).
The concentration of retinol in the kidneys of command neonates decreased by ∼80% from days 0 to 8 (β = −0.2 ± 0.0; P < 0.001). VA supplementation resulted in a significantly college kidney retinol concentration than that of the control group that lasted until day 2. At that place were no differences thereafter that resulted from treatment (Effigy 4E). Total retinol mass in kidneys remained steady (ane.8 ± 0.one nmol) in both groups, although gradual accumulation was observed during the last 10 d of the study (Figure 4F).
Other organs and the remaining carcass.
In the encephalon, VA supplementation increased retinol concentration by ∼300% from the control group value at 8 h after dosing (P < 0.001), with the difference lasting until mean solar day 1 (P < 0.05 for all) ( Figure 5A ). Retinol mass in the brain increased slightly over time (Figure 5B), but the increment was insufficient to match the rapid increment in encephalon weight (Figure 5B, inset). In BAT, VA supplementation increased retinol concentration by ∼400% from the control group value at four h (P < 0.05), and the concentration remained elevated until twenty-four hours iv (P < 0.01 for all) (Figure 5C). Retinol did not accumulate in BAT despite continuous tissue growth (Figure 5D). In WAT, the concentration of retinol was still significantly elevated from that of the control group at twenty-four hour period 18 afterward dose administration (P < 0.01) and declined gradually over the last 10 d of the study (Figure 5E). Retinol did not accumulate in WAT over time, and WAT weight did non significantly increase (Figure 5F). In the skin, VA supplementation increased total retinol concentration from that of the command group for ≤15 h after dose administration (P < 0.001) (Figure 5G). Retinol mass in the skin increased over fourth dimension past ∼500% in both groups (βcommand = 0.5 ± 0.0; βVA = 0.4 ± 0.ane; P < 0.001 for both) (Figure 5H) in parallel to the increase in skin weight (Figure 5H, inset).
Brain (A, B), WAT (C, D), BAT (E, F), pare (G, H), and carcass (I, J) total (unesterified + esterified) retinol concentration and mass, respectively, in control and VA-supplemented neonatal rats between postnatal days 4 and 28. Insets evidence the first 24 h later on dose administration (A, C, East, M, I) and organ weights (B, D, F, H, J). Each point represents the mean ± SEM of 4 rats. *P < 0.05. BAT, brown adipose tissue; VA, vitamin A; WAT, white adipose tissue.
In the carcass, the concentration of retinol was low (0.1 ± 0.0 nmol/g) and declined over time (except for day 24 in the VA-supplemented neonates), with no significant difference past treatment at whatever time during the study ( Figure 6A ). Retinol mass in the carcass was too low (0.7 ± 0.1 nmol) and declined over time (except for day 24 in the VA-supplemented grouping) despite a ∼900% increment in carcass weight (Figure 6B, inset).
Carcass total (unesterified + esterified) retinol concentration (A) and retinol mass (B) in control and VA-supplemented neonatal rats between postnatal days 4 and 28. Insets show the offset 24 h after dose administration (A) and carcass weight (B). Each signal represents the mean ± SEM of four rats. VA, vitamin A.
Discussion
This study provides comprehensive and, to our cognition, novel data on the distribution of VA in tissues of neonatal rats raised nether VA-marginal conditions. Previous studies examined the kinetics of VA administered orally to neonatal rats on postnatal day 4 and showed that ∼51% of the whole-body VA mass resided in the extrahepatic tissues (compared with ∼44% in developed rats) (14). In these experiments, withal, total retinol mass in extrahepatic tissues was not measured directly just was predicted using mathematical modeling based on tracer kinetics in plasma and tissues. Furthermore, several extrahepatic tissues, including skin, brain, and adipose tissue, were lumped together with the carcass. We analyzed these tissues individually herein, leaving simply the skeleton, muscle, and some connective tissue every bit the remaining carcass.
Based on previous findings, we hypothesized that the extrahepatic tissues in neonates would comprise a relatively college proportion of the whole-torso VA than that observed in adults and that VA supplementation would increase the proportion present in the liver. Our findings did not support these hypotheses. Instead, the results demonstrated that, despite a liver retinol concentration that would be categorized as deficient, nearly VA reserves were even so hepatic. VA supplementation had a transient event on retinol concentrations in all extrahepatic tissues examined except WAT, but the supplementation did non affect tissue retinol distribution.
VA body distribution in the command neonates.
The liver independent ∼76% of the whole-body VA mass in control pups anile 4–viii d, a proportion similar to the 86% of hepatic retinol found in adult rats and humans in the VA-adequate state (21, 22). This relatively high proportion of hepatic retinol was maintained despite a liver retinol concentration that was deficient and significantly lower than that measured in adult mother rats fed the VA-marginal nutrition ( Figure 7 ), a finding consistent with the low neonatal liver retinol concentration constitute in piglets fed a VA-complimentary diet (∼25 nmol/g) and in newborn humans (five, 23).
Mean organ full (unesterified + esterified) retinol concentration (A) and mass (B) in control and VA-supplemented rats between postnatal days 4 and 8 (0–4 d later VA supplementation). Each bar represents the hateful ± SEM of 32 rats, P < 0.05. Adult liver retinol concentration in A represents the mean ± SEM of 4 mother rats used in the study. *P < 0.05. BAT, brown adipose tissue; VA, vitamin A.
The lungs and kidneys together stored ∼5% of the whole-torso VA and showed a relatively high retinol concentration consistent with the previously demonstrated part of these organs in VA storage and metabolism in rodents. Interestingly, our study showed that rats in the control group accumulated retinol in the lungs for the 22 d of this study despite the VA-marginal atmospheric condition. This trend may reflect the need for retinol in the lungs to back up the procedure of secondary alveolar septation, which in rats occurs from postnatal days 1 to 14, dissimilar in humans, in whom this process is completed during gestation (24).
The remaining extrahepatic tissues each contributed <ane% to the full VA mass in the torso, except the skin, digestive organs, and carcass. The skin contained ∼6% of the whole-body VA mass, mostly considering of its large weight (∼20% of the whole-body weight in pups aged 4–8 d) rather than loftier retinol concentration (∼i nmol/g). Given the large surface:body weight ratio in newborns (25) and the importance of VA for the differentiation of cells in epithelial layers (26), it is possible that neonates accept a greater requirement for VA in supporting normal skin development. The skin may also act as a reservoir of VA in neonates, in which WAT is most absent. The stomach and intestine each contained ∼5% of the whole-body VA mass. These organs, all the same, were analyzed together with their contents, which contributed to the measurement. The carcass, which constituted 40% of the whole-body weight, contained only i.ii% of the whole-body retinol mass and, together with the brain, had the lowest VA concentration (∼0.1 nmol/g).
Collectively, our results show that the extrahepatic nondigestive organs in command neonates independent ∼13% of the whole-body VA mass, a proportion similar to that observed under VA-acceptable conditions. In adult VA-sufficient rats, fourteen% of the whole-body VA mass was extrahepatic (compared with 44% in VA-marginal and 93% in VA-deficient developed rats) (27–29). In humans, the corresponding pct nether VA-adequate conditions was ∼10% (30). The fact that neonates in our study stored only ∼13% of retinol outside of the liver suggests that the nonhepatic tissues may not be sufficiently adult to store VA at the adult capacity. Although the retinoid receptors, cellular retinoid-bounden proteins, and enzymes involved in retinol storage are expressed early on in life (13), they may not be rate-limiting.
The low VA content in extrahepatic tissues may be attributed to the specific characteristics of the neonatal body, particularly the scarcity of WAT. WAT, which normally constitutes five–10% of the adult rat's trunk weight (31), was nearly absent before postnatal day 12 in neonatal rats and thereafter contained only ∼one% of the whole-body VA mass, compared with ten–20% in developed rats (32, 33). BAT was present from nascence, but its contribution was besides low (∼0.v%), as was the concentration of retinol in the WAT and BAT of neonates (∼2 nmol/m compared with 21–25 nmol/g in adult rats) (34). Such low VA storage capacity of adipose tissue may be caused by the lower lipid and higher water content of neonatal tissues in general (25).
The effect of VA supplementation.
Supplementation with VA resulted in a pronounced 1–4-fold increase in retinol concentrations in nondigestive organs between 4 and 15 h after dose administration. These elevated concentrations returned to baseline within 24 h after dose assistants in plasma and all organs except the kidney, liver, WAT, and BAT ( Table i ). In kidneys, the meaning height lasted for 2 d, most probable considering of an increased rate of retinol disposal after supplementation. A iv- and eleven-d long elevation was observed in BAT and in the liver, respectively. WAT was the only organ in which the supplementation event lasted for longer than in the liver (18 d), indicating that it may serve as a long-term VA storage depot. This finding further suggests that the scarcity of WAT in neonates may predispose them to a depression VA condition.
Tabular array 1
Result of supplementation on organ VA concentration in neonatal rats administered 50,000 IU VA on postnatal day fourone
| Organ | Fourth dimension of peak VA concentration, h | Increase from control group concentration at summit, % | P | Supplementation consequence elapsing,2 h |
| Plasma | ane | 417 | 0.128 | 0 |
| Carcass | i | 350 | 0.144 | 0 |
| Tummy | 0.5 | 4551 | <0.001 | 1 |
| Peel | 4 | 295 | <0.01 | 15 |
| Intestine | 1 | 944 | <0.05 | 24 |
| Lungs | fifteen | 171 | <0.05 | 24 |
| Brain | 8 | 327 | <0.001 | 24 |
| Kidneys | 15 | 133 | <0.01 | 48 |
| BAT | 4 | 429 | <0.05 | 96 |
| Liver | 24 | 302 | <0.001 | 264 |
| WAT3 | — | — | — | 432 |
The return of plasma VA concentration to a marginal level in the supplemented pups despite a simultaneous increment in liver VA concentration suggests that neonates may have a lower "set up point" for plasma retinol, which does not necessarily point deficiency. The rapid (inside <24 h) decline of VA concentrations in all other organs suggests that they have a relatively depression VA retention capacity and apply it locally or release it back to plasma for transfer to the liver. This finding agrees with the early and transient (∼24 h) superlative in retinol concentration in the lungs, spleen, and adrenal gland of neonatal piglets aged 28 d administered 50,000 IU VA (35). From these results, Riabroy and Tanumihardjo (35) concluded that extrahepatic tissues in neonates rely on recently ingested chylomicron retinyl esters as the chief source of VA, making a abiding supply of VA in the mother'south milk or diet necessary for maintaining a steady extrahepatic VA concentration.
VA supplementation did non affect the rank lodge of tissues in terms of their retinol mass or concentration, except for the college position of stomach and intestine relative to skin (retinol mass) and kidneys (retinol concentration), as is expected from the presence of the VA dose in these organs (Figure vii). This observation was similar to findings in neonatal piglets, in which the liver ranked as the highest in terms of retinol concentration, followed by the kidneys and lungs, irrespective of VA treatment (23). Withal, kinetic studies in rats supplemented with VARA have shown a dramatic stimulatory effect of supplementation on the uptake and retention of retinyl esters by the lungs and intestine (14, 36), consistent with the previously demonstrated part of retinoic acid in upregulating genes responsible for VA storage (37–39). Based on these results, we speculate that VA alone may not exist as constructive every bit VARA in promoting extrahepatic retinol deposition, although futurity kinetic analyses of our information are needed to confirm this hypothesis.
In conclusion, our study demonstrated that male and female person Sprague-Dawley neonatal rats raised under VA-marginal weather stored most of their VA in the liver despite its scarce retinol concentration, an effect that may be explained past the low VA storage chapters of extrahepatic tissues. Nosotros also showed that supplementation with VA in a dose equivalent to that given to human newborns caused a transient increase in retinol concentration in all extrahepatic organs except WAT. This may bespeak that the scarcity of subcutaneous fat in neonates predisposes them to VA deficiency. These findings also suggest that a more than frequent VA supplementation, forth with an improved dietary intake, may be necessary to meet the needs of speedily developing neonatal tissues. More research is needed, yet, to examine the link betwixt VA storage in adipose tissue and other extrahepatic organs and the health benefits of VA supplementation.
Acknowledgments
JKH conducted the research, analyzed the data, and wrote the manuscript; LT designed and conducted the enquiry; MHG designed the research; and ACR designed and conducted the research and had main responsibility for the final content. All authors read and approved the concluding manuscript.
Footnotes
5Abbreviations used: BAT, brown adipose tissue; UPLC, ultra-performance liquid chromatography; VA, vitamin A; VARA, VA admixed with retinoic acid; WAT, white adipose tissue.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037875/
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