Submitted on April 26, 2007
Accepted on December 4, 2007
SPLANCHNIC SEQUESTRATION OF AMINO ACIDS IN AGED RATS: IN VIVO AND EX VIVO EXPERIMENTS USING A MODEL OF ISOLATED PERFUSED LIVER
Marion Jourdan1, Luc Cynober2*, Christophe Moinard1, Marie Celine Blanc3, Nathalie Neveux3, Jean-Pascal De Bandt3, and Christian Aussel4
1 Laboratory of Biological Nutrition EA 2498, Rene Descartes Paris 5 University, Paris, France
2 Clinical Chemistry, Hotel-Dieu Hospital (AP-HP), Paris, France; Laboratory of Biological Nutrition EA 2498, Rene Descartes Paris 5 University, Paris, France
3 Laboratory of Biological Nutrition EA 2498, Rene Descartes Paris 5 University, Paris, France; Clinical Chemistry, Hotel-Dieu Hospital (AP-HP), Paris, France
4 Biology Laboratory, Emile Roux Hospital (AP-HP), Paris, France; Laboratory of Biological Nutrition EA 2498, Rene Descartes Paris 5 University, Paris, France
* To whom correspondence should be addressed. E-mail: luc.cynober{at}univ-paris5.fr.
Background: Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of this study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA, and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism per se.
Materials and methods: Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or a high-protein diet (27%) for two weeks. Nitrogen balance (NB) was calculated daily. On Day 14, livers were isolated and perfused (IPL) for 90 min to study AA and urea fluxes.
Results: NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored it to adult levels. IPL from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (versus uptake in adult rats) and a hepatic accumulation of alanine.
Discussion: The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.
