Hepatic Fgf21 Expression Is Repressed after Simvastatin Treatment in Mice
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 treat...
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| Tác giả chính: | , , |
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| Ngôn ngữ: | English |
| Năm xuất bản: |
Public Library of Science (PLoS)
2018
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| Chủ đề: | |
| Truy cập Trực tuyến: | http://lrc.quangbinhuni.edu.vn:8181/dspace/handle/DHQB_123456789/3849 |
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| Tóm tắt: | 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 realtime
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. |
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