Citrulline reduces glyceroneogenesis and induces fatty acid release in visceral adipose tissue from overweight rats

Mol Nutr Food Res. 2014 Dec;58(12):2320-30. doi: 10.1002/mnfr.201400507. Epub 2014 Oct 31.


Scope: High-fat diet (HFD) increases visceral adipose tissue (AT). Our aim was to evaluate whether citrulline (CIT) affected nonesterified fatty acid (NEFA) metabolism in AT from HFD-fed rats.

Methods and results: Rats were fed for 8 weeks with either a control diet (CD) or HFD. Retroperitoneal AT explants were exposed to 2.5 mmol/L CIT for 24 h. We analyzed lipolysis, beta-oxidation, glyceroneogenesis, and the expression of the key associated enzymes. CIT doubled NEFA release selectively in HFD AT. Phosphorylation of hormone-sensitive lipase was upregulated 50 and 100% by CIT in CD and HFD AT, respectively. Under CIT, beta-oxidation increased similarly whatever the diet, whereas glyceroneogenesis, which permits NEFA re-esterification, was downregulated 50 and 80% in CD and HFD AT, respectively. In the latter, the important decrease in re-esterification probably explains the rise of NEFA release. A pretreatment with the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester abolished CIT effects.

Conclusion: These results demonstrate direct lipolytic and antiglyceroneogenic effects of CIT on CD and HFD AT. The selective CIT-mediated NEFA release from HFD AT was probably the consequence of the drastic decrease in glyceroneogenesis and nitric oxide was a mediator of CIT effects. These results provide evidence for a direct action of CIT on AT to reduce overweight.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrulline / pharmacology*
  • Diet, High-Fat / adverse effects
  • Fatty Acids, Nonesterified / metabolism*
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism
  • Lipogenesis / drug effects*
  • Lipolysis / drug effects
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / metabolism
  • Overweight / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sterol Esterase / metabolism


  • Fatty Acids, Nonesterified
  • Citrulline
  • Nitric Oxide Synthase
  • Sterol Esterase
  • NG-Nitroarginine Methyl Ester