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

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 HFDfed 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, betaoxidation 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 -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 consequenceofthedrasticdecreaseinglyceroneogenesisandnitricoxidewasamediatorofCIT effects. These results provide evidence for a direct action of CIT on AT to reduce overweight.