Faculty Publications

Document Type

Article

Publication Date

January 2007

Publication Title

Journal of Lipid Research

Volume

48

First Page

904

Last Page

913

DOI

10.1194/jlr.M600528-JLR200

Keywords

hyporetinoelmia, kinetic analysis, retinol, Windows version of Simulation, Analysis, Modeling Software

Disciplines

Food Science | Nutrition

Abstract

Vitamin A (VA) kinetics was studied in rats with marginal VA stores before, during, and after inflammation. Rats received orally [11,12-3H(N)]retinol ([3H]VA; day 0), and inflammation was induced on day 21 with lipopolysacchride (LPS) for 3 days (n = 5) or recombinant human interleukin-6 (rhIL-6) for 7 days (n = 5). Both the fraction of [3H]VA and retinol concentrations in plasma were reduced significantly by LPS or rhIL-6. Compartmental analysis using the Windows version of Simulation, Analysis, and Modeling software was applied to group mean data, and non-steady-state models were developed. After absorption, VA kinetics was described by a three-compartment model that included plasma, kidney/interstitium, and liver/carcass. Four mechanisms decreasing plasma retinol were investigated: increased urinary excretion, increased irreversible loss, increased movement into interstitium, and decreased hepatic mobilization. Modeling demonstrated that a 79% reduction in hepatic mobilization of retinol (from 4.3 to 0.9 nmol/h) by 15 h after LPS best accounted for the observed changes in plasma VA kinetics (sum of squares = 9.05 × 10−07). rhIL-6 caused an earlier reduction (75% by 5.6 h). These models predicted a return to control values by 10 days after inflammation. If prolonged, inflammation-induced hyporetinolemia can render hepatic retinol unavailable to extrahepatic tissues, possibly leading to their impaired function, as observed in VA-deficient children with measles infection.

Comments

This research was originally published in Journal of Lipid Research. Sin H. Gieng, Michael H. Green, Joanne B. Green, and Francisco J. Rosales. Details for Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats. Journal of Lipid Research. 2007; 48:904-913. © The American Society for Biochemistry and Molecular Biology.
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