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Am J Physiol Endocrinol Metab (April 11, 2006). doi:10.1152/ajpendo.00398.2005
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Submitted on August 24, 2005
Accepted on March 30, 2006

Citrulline modulates muscle protein metabolism in old malnourished rats

Sylwia Osowska1, Thierry Duchemann2, Stephane Walrand3, Alexandre Paillard2, Yves Boirie3, Luc Cynober4, and Christophe Moinard2*

1 Laboratoire de Biologie de la Nutrition, FAculte de Pharmacie, Paris, France
2 LAboratoire de Biologie de la Nutrition, FAculte de Pharmacie, Paris, France
3 Laboratoire de Nutrition Humaine, UMPE, INRA, Clermont Ferrand, France
4 LAboratoire de Biologie de la Nutrition, FAculte de Pharmacie, Paris, France; LAboratoire de Biochimie, AP-HP, Hotel Dieu, Paris, France

* To whom correspondence should be addressed. E-mail: christophe.moinard{at}univ-paris5.fr.

Protein-energy malnutrition is common in the elderly. 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 less 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-months) rats were submitted to dietary restriction (50 % of the food intake) during 12 weeks. They were randomized into 3 groups: 10 rats (R) were killed and 20 other refed (90 % of the food intake) for 1 week with a standard diet (NEAA) or a citrulline-supplemented diet (Cit group). Before the sacrifice the rats were injected with 13C Valine and the absolute protein synthesis rate (ASR) was measured in the tibialis. 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 nor on the muscle protein content. 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). A realistic therapeutic approach is proposed to improve muscle protein content in the muscle in frail state related to malnutrition in ageing.




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