title: Citrulline reduces glyceroneogenesis and induces fatty acid release in visceral adipose tissue from overweight rats.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Joffin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jaubert
authors.forename: Sylvie
authors.initials: S
authors.lastname: Durant
authors.forename: Jean
authors.initials: J
authors.lastname: Bastin
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: De Bandt
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.forename: Christophe
authors.initials: C
authors.lastname: Moinard
authors.forename: Xavier
authors.initials: X
authors.lastname: Coumoul
authors.forename: Claude
authors.initials: C
authors.lastname: Forest
authors.forename: Philippe
authors.initials: P
authors.lastname: Noirez
mesh_terms: D000818:Animals; D002956:Citrulline / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D050177:Overweight / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D002787:Sterol Esterase / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D002956:Citrulline; D019001:Nitric Oxide Synthase; D002787:Sterol Esterase; D019331:NG-Nitroarginine Methyl Ester
keywords: Adipose tissue; Citrulline; Fatty acids; Glyceroneogenesis; Overweight