Dataset Information

Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats.

ABSTRACT: Little is known about the contribution of different tissues to whole-body vitamin A (VA) kinetics in neonates. Here, we have used model-based compartmental analysis of tissue tracer kinetic data from unsupplemented (control) and VA-retinoic acid (VARA)-supplemented neonatal rats to determine VA kinetics in specific tissues under control and supplemented conditions. First, compartmental models for retinol kinetics were developed for individual tissues, and then an integrated compartmental model incorporating all tissues was developed for both groups. The models predicted that 52% of chylomicron (CM) retinyl ester was cleared by liver in control pups versus 22% in VARA-treated pups, whereas about 51% of VA was predicted to be extrahepatic in 4- to 6-day-old unsupplemented neonatal rats. VARA increased CM retinyl ester uptake by lung, carcass, and intestine; decreased the release into plasma of retinol that had been cleared by liver and lung as CM retinyl esters; stimulated the uptake of retinol from plasma holo-retinol binding protein into carcass; and decreased the retinol turnover out of the liver. Overall, neonatal VA trafficking differed from that previously described for adult animals, with a larger contribution of extrahepatic tissues to CM clearance, especially after VA supplementation, and a significant amount of VA distributed in extrahepatic tissues.

SUBMITTER: Tan L

PROVIDER: S-EPMC4109768 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats.

Tan Libo L Wray Amanda E AE Green Michael H MH Ross A Catharine AC

Journal of lipid research 20140609 8

Little is known about the contribution of different tissues to whole-body vitamin A (VA) kinetics in neonates. Here, we have used model-based compartmental analysis of tissue tracer kinetic data from unsupplemented (control) and VA-retinoic acid (VARA)-supplemented neonatal rats to determine VA kinetics in specific tissues under control and supplemented conditions. First, compartmental models for retinol kinetics were developed for individual tissues, and then an integrated compartmental model i ...[more]

PMID: 24914038

Similar Datasets

Project description:BackgroundModel-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans.ObjectivesWe applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines.MethodsChildren ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data.ResultsModel-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9-17 mo), Filipino (12-18 mo), and Guatemalan children (35-65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2-3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively).ConclusionsBy collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).

Project description:BACKGROUND:Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. OBJECTIVE:With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. DESIGN:Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7-compartment model. RESULTS:Subjects absorbed a mean ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P < 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 ± 7 and 48 ± 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis-lycopene isomerization was predictive of plasma (13)C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% ± 6%) and all-trans (23.2% ± 8%) isomers did not differ, endogenous isomerization (0.97 ± 0.25 ?mol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. CONCLUSION:(13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.

Project description:Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula) and last but not least, the diet composition. In the diet composition, protein and carbohydrate are very important for the growth of microbiota, many infant fomulas (different ratio protein/carbohydrate) can regulate the development of gut microbiota by different metabolism. The effect of low-protein, high-carbohydrate infant formula on the establishment of microbiota remains unclear, and the effect of human breast milk on the gut microbiota of the rats has also not been reported.In a 7 d intervention, a total of 36 neonatal SD rats (14 d old) were randomly assigned to the following groups: (1) breast-fed group (A group); (2) low-protein, high-carbohydrate infant formula-fed group (B group); (3) human breast milk-fed group (C group). After 7 days, we selected 6 rats at random from each group to study. Microbial composition in the contents of the large intestines was analysed by Miseq Sequencing. Significantly different (p<0.05) microbial colonisation patterns were observed in the large intestines of breast-fed group from low-protein, high-carbohydrate infant formula-fed and human breast milk-fed rats, but the microbiota of low-protein, high-carbohydrate infant formula-fed group and human breast milk-fed group have high similarity. At the phylum level, the absolute quantity of Bacteroidetes, Firmicutes and Proteobacteria (p<0.001) significantly differentiated in breast-fed group from low- protein, high- carbohydrate infant formula-fed and human breast milk-fed groups. Lachnospiraceae, Bacteroidaceae, Porphyromonadaceae and Prevotellaceae were the 4 top families in breast-fed group, but the top 4 families in low-protein, high- carbohydrate infant formula-fed and human breast milk-fed groups were the same, which were Bacteroidaceae, Enterobacteriaceae, Porphyromonadaceae and Lachnospiraceae. At the genus level, Bacteroides was the most abundant division, their OTUS abundance in three groups was 14.91%, 35.94%, 43.24% respectively.This study showed that infant formula closer resembling human milk was more different than rats' breast milk and led to a microbiota profile similar to that for human breast milk-fed neonates. The finding could support a new thinking to develop infant formulas, and provide much more details than what is known previously.

Project description:BackgroundPublic health nutritionists need accurate and feasible methods to assess vitamin A status and to evaluate efficacy of interventions, especially in children. The application of population-based designs to tracer kinetic data is an effective approach that reduces sample burden for each child.ObjectivesObjectives of the study were to use theoretical data to validate a population-based (super-child) approach for estimating group mean vitamin A total body stores (TBS) and retinol kinetics in children and to use population-based data to improve individual TBS predictions using retinol isotope dilution (RID).MethodsWe generated plasma retinol kinetic data from 6 h to 56 d for 50 theoretical children with high vitamin A intakes, assigning values within physiologically reasonable ranges for state variables and kinetic parameters ("known values"). Mean data sets for all subjects at extensive (n = 36) and reduced (n = 11) sampling times, plus 5 data sets for reduced numbers (5/time, except all at 4 d) and times, were analyzed using Simulation, Analysis and Modeling software. Results were compared with known values; population RID coefficients were used to calculate TBS for individuals.ResultsFor extensive and reduced data sets including all subjects, population TBS predictions were within 1% of the known value. For 5 data sets reflecting numbers and times being used in ongoing super-child studies, predictions were within 1-17% of the known group value. Using RID equation coefficients from population modeling, TBS predictions at 4 d were within 25% of the known value for 66-80% of subjects and reflected the range of assigned values; when ranked, predicted and assigned values were significantly correlated (Rs = 0.93, P < 0.0001). Results indicate that 7 d may be better than 4 d for applying RID in children. For all data sets, predictions for kinetic parameters reflected the range of known values.ConclusionThe population-based (super-child) approach provides a feasible experimental design for quantifying retinol kinetics, accurately estimating group mean TBS, and predicting TBS for individuals reasonably well.

Dataset Information

Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats.

Publications

Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets