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

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


Scope: 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.

Methods and results: 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.

Conclusion: 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.

Keywords: Adipose tissue; Aging; Citrulline; Fatty acids; Glyceroneogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Age Factors
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Cells, Cultured
  • Citrulline / pharmacology*
  • Fatty Acids / metabolism*
  • Gene Expression Regulation / drug effects
  • Inflammation / genetics
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Organ Culture Techniques
  • Oxidation-Reduction
  • PPAR gamma / genetics
  • Rats, Sprague-Dawley


  • Fatty Acids
  • PPAR gamma
  • Citrulline
  • Carnitine O-Palmitoyltransferase