Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism

Christopher J. Cifelli, Joanne Balmer Green, Michael Henry Green

Research output: Chapter in Book/Report/Conference proceedingChapter

28 Citations (Scopus)

Abstract

We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.

Original languageEnglish (US)
Title of host publicationVitamin A
EditorsGerald Litwack
Pages161-195
Number of pages35
DOIs
StatePublished - Mar 16 2007

Publication series

NameVitamins and Hormones
Volume75
ISSN (Print)0083-6729

Fingerprint

Vitamin A
Fenretinide
Dietary Iron
Dioxins
Recycling
Tretinoin
Terminology
Vitamins
Small Intestine
Testis
Homeostasis

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrinology

Cite this

Cifelli, C. J., Green, J. B., & Green, M. H. (2007). Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism. In G. Litwack (Ed.), Vitamin A (pp. 161-195). (Vitamins and Hormones; Vol. 75). https://doi.org/10.1016/S0083-6729(06)75007-5
Cifelli, Christopher J. ; Green, Joanne Balmer ; Green, Michael Henry. / Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism. Vitamin A. editor / Gerald Litwack. 2007. pp. 161-195 (Vitamins and Hormones).
@inbook{623639bbc3994c3ead2017cb7e4948bd,
title = "Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism",
abstract = "We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.",
author = "Cifelli, {Christopher J.} and Green, {Joanne Balmer} and Green, {Michael Henry}",
year = "2007",
month = "3",
day = "16",
doi = "10.1016/S0083-6729(06)75007-5",
language = "English (US)",
isbn = "0127098755",
series = "Vitamins and Hormones",
pages = "161--195",
editor = "Gerald Litwack",
booktitle = "Vitamin A",

}

Cifelli, CJ, Green, JB & Green, MH 2007, Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism. in G Litwack (ed.), Vitamin A. Vitamins and Hormones, vol. 75, pp. 161-195. https://doi.org/10.1016/S0083-6729(06)75007-5

Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism. / Cifelli, Christopher J.; Green, Joanne Balmer; Green, Michael Henry.

Vitamin A. ed. / Gerald Litwack. 2007. p. 161-195 (Vitamins and Hormones; Vol. 75).

Research output: Chapter in Book/Report/Conference proceedingChapter

TY - CHAP

T1 - Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism

AU - Cifelli, Christopher J.

AU - Green, Joanne Balmer

AU - Green, Michael Henry

PY - 2007/3/16

Y1 - 2007/3/16

N2 - We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.

AB - We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.

UR - http://www.scopus.com/inward/record.url?scp=33947118627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947118627&partnerID=8YFLogxK

U2 - 10.1016/S0083-6729(06)75007-5

DO - 10.1016/S0083-6729(06)75007-5

M3 - Chapter

SN - 0127098755

SN - 9780127098753

T3 - Vitamins and Hormones

SP - 161

EP - 195

BT - Vitamin A

A2 - Litwack, Gerald

ER -

Cifelli CJ, Green JB, Green MH. Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism. In Litwack G, editor, Vitamin A. 2007. p. 161-195. (Vitamins and Hormones). https://doi.org/10.1016/S0083-6729(06)75007-5