title: Hepatic Fgf21 Expression Is Repressed after Simvastatin Treatment in Mice.
abstract: Fibroblast growth factor 21 (Fgf21) is a hormone with emerging beneficial roles in glucose and lipid homeostasis. The interest in Fgf21 as a potential antidiabetic drug and the factors that regulate its production and secretion is growing. Statins are the most widely prescribed drug for the treatment of dyslipidemia. However, the function of statins is not limited to the lowering of cholesterol as they are associated with pleiotropic actions such as antioxidant, anti-inflammatory and cytoprotective effects. The recently described effect of statins on mitochondrial function and the induction of Fgf21 by mitochondrial stress prompted us to investigate the effect of statin treatment on Fgf21 expression in the liver. To this end, C57BL6J male mice and primary mouse hepatocytes were treated with simvastatin, and Fgf21 expression was subsequently assessed by immunoblotting and quantitative real-time PCR. Hepatic Fgf21 protein and mRNA and circulating levels of FGF21significantly decreased in mice that had received simvastatin in their food (0.1% w/w) for 1 week. This effect was also observed with simvastatin doses as low as 0.01% w/w for 1 week or following 2 intraperitoneal injections within a single day. The reduction in Fgf21 mRNA levels was further verified in primary mouse hepatocytes, indicating that the effect of simvastatin is cell autonomous. In conclusion, simvastatin treatment reduced the circulating and hepatic Fgf21 levels and this effect warrants further investigation with reference to its role in metabolism.
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Panos
authors: P
authors: Ziros
authors: Department of Pharmacy, University of Patras, Patras, Greece.
authors: Zoi
authors: Z
authors: Zagoriti
authors: Department of Pharmacy, University of Patras, Patras, Greece.
authors: George
authors: G
authors: Lagoumintzis
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Venetsana
authors: V
authors: Kyriazopoulou
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Ralitsa P
authors: RP
authors: Iskrenova
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Evagelia I
authors: EI
authors: Habeos
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Gerasimos P
authors: GP
authors: Sykiotis
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Dionysios V
authors: DV
authors: Chartoumpekis
authors: Department of Internal Medicine, Division of Endocrinology, School of Medicine, University of Patras, Patras, Greece.
authors: Ioannis G
authors: IG
authors: Habeos
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D019821:Simvastatin