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J Lipid Res. 2014 Aug;55(8):1738-49. doi: 10.1194/jlr.M050518. Epub 2014 Jun 9.

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

Author information

1
Graduate Program in Nutrition, The Pennsylvania State University, University Park, PA 16802 Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802.
2
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802.
3
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802 The Huck Institutes for the Life Sciences, The Pennsylvania State University, University Park, PA 16802.

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.

KEYWORDS:

Windows version of the Simulation, Analysis, and Modeling software; chylomicrons; extrahepatic tissues; neonate; retinol

PMID:
24914038
PMCID:
PMC4109768
DOI:
10.1194/jlr.M050518
[Indexed for MEDLINE]
Free PMC Article

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