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Mol Nutr Food Res. 2014 Sep;58(9):1765-75. doi: 10.1002/mnfr.201400053. Epub 2014 Jun 10.

Citrulline induces fatty acid release selectively in visceral adipose tissue from old rats.

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Université Paris Descartes, Sorbonne Paris Cité, France; Institut National de la Santé et de la Recherche Médicale UMR-S 1124, Faculté des Sciences Fondamentales et Biomédicales, Pharmacologie Toxicologie et Signalisation Cellulaire, Paris, France.



During aging, increased visceral adipose tissue (AT) mass may result in impaired metabolic status. A citrulline (CIT)-supplemented diet reduces AT mass in old rats. We hypothesized that CIT could directly affect fatty acid (FA) metabolism in retroperitoneal AT.


A 24-h exposure of AT explants from old (25 months) rats to 2.5 mM CIT induced a 50% rise in glycerol and FA release, which was not observed in explants from young (2 months) animals. The phosphorylated form of hormone-sensitive lipase, a key lipolytic enzyme, was 1.5-fold higher in CIT-treated explants from old and young rats, whereas glyceroneogenesis, that provides glycerol-3P requested for FA re-esterification, and its key enzyme phosphoenolpyruvate carboxykinase, were down-regulated 40-70%. Specifically in young rats, beta-oxidation capacity and gene expressions of carnitine palmitoyl transferase 1-b and very long chain acyl-CoA dehydrogenase were strongly up-regulated by CIT. In contrast, in old rats, while glyceroneogenesis was lower, beta-oxidation was not affected, enabling increased FA release.


Hence, in visceral AT, CIT exerts a specific induction of the beta-oxidation capacity in young rats and a selective stimulation of FA release in old rats, therefore providing a direct mechanism of CIT action to reduce AT mass.


Adipose tissue; Aging; Citrulline; Fatty acids; Glyceroneogenesis

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