Frédéric Capel1, Gwladys Chabrier1, Elodie Pitois1, Jean-Paul Rigaudière1, Servane Le Plenier2, Christine Durand3, Chrystèle Jouve1, Jean-Pascal de Bandt2,4, Luc Cynober2,4, Christophe Moinard2, Béatrice Morio1,3. 1. INRA, UMR 1019, UNH, CRNH Auvergne and Clermont University, Auvergne University, Human Nutrition Unit, Clermont-Ferrand, France. 2. Laboratory of Nutrition Biology EA 4466, Paris-Descartes University, Paris, France. 3. INRA, UMR 1397, CarMeN Laboratory, Lyon 1 University, INSERM U1060, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France. 4. Department of Clinical Chemistry, Cochin and Hotel-Dieu Hospitals, Assistance Publique - Hôpitaux de Paris, Paris, France.
Abstract
BACKGROUND AND PURPOSE: 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). EXPERIMENTAL APPROACH: 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. KEY 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 AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: 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). EXPERIMENTAL APPROACH: C57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIOmice 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. KEY RESULTS:DIOcit-statmice 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-statmice 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-statmice compared with those of other DIO groups. CONCLUSIONS AND IMPLICATIONS: The citrulline-atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIOmice. 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: Lars P Bechmann; Rebekka A Hannivoort; Guido Gerken; Gökhan S Hotamisligil; Michael Trauner; Ali Canbay Journal: J Hepatol Date: 2011-12-13 Impact factor: 25.083
Authors: Neil J Stone; Jennifer G Robinson; Alice H Lichtenstein; C Noel Bairey Merz; Conrad B Blum; Robert H Eckel; Anne C Goldberg; David Gordon; Daniel Levy; Donald M Lloyd-Jones; Patrick McBride; J Sanford Schwartz; Susan T Shero; Sidney C Smith; Karol Watson; Peter W F Wilson Journal: J Am Coll Cardiol Date: 2013-11-12 Impact factor: 24.094