title: Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet-induced obesity.
abstract: OBJECTIVE
  NO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet-induced obesity (DIO).
  
  
  METHODS
  C57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit-stat) for 3 weeks. Thereafter, body composition, glucose tolerance, insulin sensitivity and liver fat metabolism were measured.
  
  
  RESULTS
  DIOcit-stat mice showed lower body weight, fat mass and epididymal fat depots compared with other DIO groups. Unlike other DIO groups, glucose tolerance and insulin sensitivity of DIOcit-stat, along with blood glucose and insulin concentrations in response to feeding, were restored to control values. Refeeding-induced changes in liver lipogenic activity were also reduced in DIOcit-stat mice compared with those of DIO animals. This was associated with decreased gene expression of the transcription factor SREBP-1, liver X receptor α, ChREBP and of target lipogenic enzymes in the liver of DIOcit-stat mice compared with those of other DIO groups.
  
  
  CONCLUSIONS
  The citrulline-atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIO mice. Furthermore, it potentiated inhibition of hepatic de novo lipogenesis activity. This combination has potential for preservation of glucose homeostasis in patients receiving statin therapy.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Capel
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.
authors.forename: Gwladys
authors.initials: G
authors.lastname: Chabrier
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Pitois
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Rigaudière
authors.affiliation: Laboratory of Nutrition Biology EA 4466, Paris-Descartes University, Paris, France.
authors.forename: Servane
authors.initials: S
authors.lastname: Le Plenier
authors.affiliation: INRA, UMR 1397, CarMeN Laboratory, Lyon 1 University, INSERM U1060, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Durand
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.
authors.forename: Chrystèle
authors.initials: C
authors.lastname: Jouve
authors.affiliation: Laboratory of Nutrition Biology EA 4466, Paris-Descartes University, Paris, France.|Department of Clinical Chemistry, Cochin and Hotel-Dieu Hospitals, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: de Bandt
authors.affiliation: Laboratory of Nutrition Biology EA 4466, Paris-Descartes University, Paris, France.|Department of Clinical Chemistry, Cochin and Hotel-Dieu Hospitals, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.affiliation: Laboratory of Nutrition Biology EA 4466, Paris-Descartes University, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moinard
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France.|INRA, UMR 1397, CarMeN Laboratory, Lyon 1 University, INSERM U1060, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Morio
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002956:Citrulline / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D004032:Diet; D004041:Dietary Fats; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D019422:Dietary Sucrose; D051780:Sterol Regulatory Element Binding Protein 1; D002956:Citrulline; D000069059:Atorvastatin; D055372:AMP-Activated Protein Kinases; D005947:Glucose