Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2008-03, Vol.294 (3), p.R748-R755
• Main Authors: Jourdan, M, Cynober, L, Moinard, C, Blanc, M. C, Neveux, N, De Bandt, J. P, Aussel, C
• Format: Article
• Language: English
• Subjects: Aging; Aging - metabolism; Algorithms; Amino acids; Amino Acids - metabolism; Animals; Body Weight - physiology; Coloring Agents; Diet; Dietary Proteins - metabolism; Eating - physiology; In Vitro Techniques; Indocyanine Green; Liver; Liver - metabolism; Male; Nitrogen - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Splanchnic Circulation - physiology; Studies; Urea - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00291.2007

1 Laboratory of Biological Nutrition, René Descartes Paris 5 University; 2 Clinical Chemistry, Hotel-Dieu Hospital Assistance Publique des Hopitaux de Paris, Paris; and 3 Biology Laboratory, Emile Roux Hospital Assistance Publique des Hopitaux de Paris, Limeil-Brévannes, France Submitted 26 April 2007 ; accepted in final form 4 December 2007 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 the present 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. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14 , livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. 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. aging; nitrogen metabolism; isolated perfused liver; high-protein diet Address for reprint requests and other correspondence: L. Cynober, Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4 Ave. de l'Observatoire, 75270 Paris cedex 06, France (e-mail: luc.cynober{at}htd.aphp.fr )