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Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity
Author(s) -
Capel Frédéric,
Chabrier Gwladys,
Pitois Elodie,
Rigaudière JeanPaul,
Plenier Servane Le,
Durand Christine,
Jouve Chrystèle,
Bandt JeanPascal,
Cynober Luc,
Moinard Christophe,
Morio Béatrice
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13269
Subject(s) - medicine , endocrinology , glucose homeostasis , atorvastatin , lipogenesis , diet induced obese , insulin tolerance test , homeostasis , insulin , energy homeostasis , carbohydrate metabolism , insulin resistance , lipid metabolism , chemistry , obesity , insulin sensitivity
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.