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Am J Physiol Endocrinol Metab 291: E582-E586, 2006. First published April 11, 2006; doi:10.1152/ajpendo.00398.2005
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Citrulline modulates muscle protein metabolism in old malnourished rats

S. Osowska,1 T. Duchemann,1 S. Walrand,2 A. Paillard,1 Y. Boirie,2 L. Cynober,1,3 and C. Moinard1

1Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, Université Paris 5; 2UMPE, Laboratoire de la Nutrition Humaine, Clermont-Ferrand; and 3Laboratoire Biochimie A, Hôtel-Dieu, Assistance Publique des Hopitaux de Paris, Paris, France

Submitted 24 August 2005 ; accepted in final form 30 March 2006

Protein energy malnutrition is common in the elderly, especially in hospitalized patients. The development of strategies designed to correct such malnutrition is essential. Our working hypothesis was that poor response to nutrition with advancing age might be related to splanchnic sequestration of amino acids, which implies that fewer amino acids reach the systemic circulation. Administration of citrulline, which is not taken up by the liver, can offer a means of increasing whole body nitrogen availability and, hence, improve nutritional status. Thirty old (19 mo) rats were submitted to dietary restriction (50% of food intake) for 12 wk. They were randomized into three groups: 10 rats (R group) were killed and 20 others refed (90% of food intake) for 1 wk with a standard diet (NEAA group) or a citrulline-supplemented diet (Cit group). Before being killed, the rats were injected with [13C]valine, and the absolute protein synthesis rate (ASR) was measured in the tibialis using the flooding-dose method. When the rats were killed, the tibialis was removed for protein content analysis. Blood was sampled for amino acid and insulin analysis. The standard diet did not have any effect on protein synthesis or on the protein content in the muscle. Citrulline supplementation led to higher protein synthesis and protein content in muscle (117 ± 9, 120 ± 14, and 163 ± 4 mg/organ for protein content in R, NEAA, and Cit groups, P < 0.05). The ASR were 0.30 ± 0.04, 0.31 ± 0.04, and 0.56 ± 0.10 mg/h in the three groups, respectively (R and NEAA vs. Cit, P < 0.05). Insulinemia was significantly higher in the Cit group. For the first time, a realistic therapeutic approach is proposed to improve muscle protein content in muscle in frail state related to malnutrition in aging.

sarcopenia; malnutrition; protein synthesis



Address for reprint requests and other correspondence: C. Moinard, Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, Université Paris 5, 4 Ave. de l'Observatoire, 75270 Paris cedex 06, France (christophe.moinard{at}univ-paris5.fr)




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