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

Libo Tan, Amanda E. Wray, Michael H. Green, A. Catharine Ross

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 VARAtreated 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 holoretinol 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.

Original languageEnglish (US)
Pages (from-to)1738-1749
Number of pages12
JournalJournal of Lipid Research
Volume55
Issue number8
DOIs
StatePublished - Aug 2014

Fingerprint

Tretinoin
Vitamin A
Vitamins
Rats
Kinetics
Chylomicrons
Tissue
Liver
Esters
Plasma Retinol-Binding Proteins
Lung
Intestines
Animals
Plasmas

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

@article{6fb0ce31a6204d59aae53ed092d49680,
title = "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 VARAtreated 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 holoretinol 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.",
author = "Libo Tan and Wray, {Amanda E.} and Green, {Michael H.} and Ross, {A. Catharine}",
year = "2014",
month = "8",
doi = "10.1194/jlr.M050518",
language = "English (US)",
volume = "55",
pages = "1738--1749",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "8",

}

Compartmental modeling of whole-body vitamin a kinetics in unsupplemented and vitamin a-retinoic acid-supplemented neonatal rats. / Tan, Libo; Wray, Amanda E.; Green, Michael H.; Ross, A. Catharine.

In: Journal of Lipid Research, Vol. 55, No. 8, 08.2014, p. 1738-1749.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Compartmental modeling of whole-body vitamin a kinetics in unsupplemented and vitamin a-retinoic acid-supplemented neonatal rats

AU - Tan, Libo

AU - Wray, Amanda E.

AU - Green, Michael H.

AU - Ross, A. Catharine

PY - 2014/8

Y1 - 2014/8

N2 - 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 VARAtreated 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 holoretinol 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.

AB - 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 VARAtreated 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 holoretinol 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.

UR - http://www.scopus.com/inward/record.url?scp=84905026194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905026194&partnerID=8YFLogxK

U2 - 10.1194/jlr.M050518

DO - 10.1194/jlr.M050518

M3 - Article

C2 - 24914038

AN - SCOPUS:84905026194

VL - 55

SP - 1738

EP - 1749

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 8

ER -