title: Citrulline Supplementation Induces Changes in Body Composition and Limits Age-Related Metabolic Changes in Healthy Male Rats.
abstract: BACKGROUND
  Aging is associated with profound metabolic disturbances, and citrulline may be of use to limit them.
  
  
  OBJECTIVE
  The aim of this work was to evaluate the long-term effect of citrulline supplementation on metabolism in healthy aged rats.
  
  
  METHODS
  Twenty-month-old male rats were randomly assigned to be fed (ad libitum) for 12 wk with either a citrulline-enriched diet (1 g ⋅ kg(-1) ⋅  d(-1)) or a standard diet [rendered isonitrogenous by addition of nonessential amino acids (NEAAs)]. Motor activity and muscle strength were measured, body composition was assessed, and muscle metabolism (protein structure, mitochondrial exploration, and transductional factors) and lipid metabolism (lipoprotein composition and sensitivity to oxidative stress) were explored.
  
  
  RESULTS
  Compared with the NEAA-treated group, citrulline supplementation was associated with lower mortality (0% vs. 20%; P = 0.05), 9% higher lean body mass (P < 0.05), and 13% lower fat mass (P < 0.05). Compared with the NEAA-treated group, citrulline-treated rats had greater muscle mass (+14-48% depending on type of muscle; P < 0.05 for tibialis, gastrocnemius, and plantaris). Susceptibility to oxidation of lipoproteins, as measured by the maximal concentration of 7-ketocholesterol after copper-induced VLDL and LDL oxidation, was lower in citrulline-treated rats than in NEAA-treated rats (187 ± 8 μmol/L vs. 243 ± 7 μmol/L; P = 0.0005).
  
  
  CONCLUSIONS
  Citrulline treatment in male aged rats favorably modulates body composition and protects against lipid oxidation and, thus, emerges as an interesting candidate to help prevent the aging process.
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466, christophe.moinard@parisdescartes.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moinard
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466.
authors.forename: Servane
authors.initials: S
authors.lastname: Le Plenier
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466.
authors.forename: Philippe
authors.initials: P
authors.lastname: Noirez
authors.affiliation: National Institute for Agronomic Research, Mixed Research Unit 1019, Human Nutrition Unit, Human Nutrition Research Center Auvergne and Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France;
authors.forename: Béatrice
authors.initials: B
authors.lastname: Morio
authors.affiliation: Faculty of Pharmaceutical and Biological Sciences, University Paris Descartes, Sorbonne Paris Cité, Paris, France; Public Assistance of Parisian Hospital (AP-HP), Hôpitaux Universitaires Hôpital Pitié-Salpêtrière-Charles Foix, Service de Biochimie Métabolique, Paris, France;
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.affiliation: Animalerie Centrale, Faculté des Sciences Pharmaceutiques et Biologiques de l'Université Paris Descartes, Paris, France;
authors.forename: Caroline
authors.initials: C
authors.lastname: Kharchi
authors.affiliation: National Institute for Medical Research U974, National Scientific Research Center, Mixed Research Unit 7215, Institut de Myologie, Université Pierre et Marie Curie, Université Paris Descartes, Paris, France;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466, Service Biochimie Interhospitalier Hôtel-Dieu et Cochin, Public Assistance of Parisian Hospital, Paris, France; and.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Neveux
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466, Service Biochimie Interhospitalier Hôtel-Dieu et Cochin, Public Assistance of Parisian Hospital, Paris, France; and.
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.affiliation: Department of Experimental, Metabolic, and Clinical Biology, EA 4466, Département de Gériatrie, Hôpitaux Universitaires Bichat et Beaujon, AP-HP, Faculté de Médecine Paris Diderot, Paris, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Raynaud-Simon
mesh_terms: D000375:Aging / Q000187:drug effects; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000097:blood; D002956:Citrulline / Q000494:pharmacology*; D019587:Dietary Supplements; D007653:Ketocholesterols; D050356:Lipid Metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D000596:Amino Acids; D008076:Cholesterol, HDL; D007653:Ketocholesterols; D046912:Multiprotein Complexes; D014280:Triglycerides; D002956:Citrulline; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C003001:7-ketocholesterol
keywords: aging; amino acids; body composition; lipoprotein; muscle; protein metabolism