論文

2017年4月

Effects of K-877, a novel selective PPARα modulator, on small intestine contribute to the amelioration of hyperlipidemia in low-density lipoprotein receptor knockout mice.

Journal of pharmacological sciences
  • Kenta Takei
  • ,
  • Yoshimi Nakagawa
  • ,
  • Yunong Wang
  • ,
  • Song-Iee Han
  • ,
  • Aoi Satoh
  • ,
  • Motohiro Sekiya
  • ,
  • Takashi Matsuzaka
  • ,
  • Hitoshi Shimano

133
4
開始ページ
214
終了ページ
222
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jphs.2017.02.003

Peroxisome proliferator-activated receptor α (PPARα) is a well-known therapeutic target for treating hyperlipidemia. K-877 is a novel selective PPARα modulator (SPPARMα) that enhances PPARα transcriptional activity with high selectivity and potency, resulting in reduced plasma lipid levels. This study aimed to evaluate the effects of K-877 on hyperlipidemia in low-density lipoprotein receptor knockout (Ldlr-/-) mice, a mouse model of atherosclerosis. We revealed that K-877 administration significantly decreased plasma triglyceride (TG) and total cholesterol (TC) levels and increased plasma high-density lipoprotein cholesterol (HDL-C) levels in Ldlr-/- mice. K-877 administration to Ldlr-/- mice efficiently increased the gene expression of PPARα and its target genes related to fatty acid oxidation in the liver and small intestine. The same treatment significantly increased ATP-binding cassette a1 gene expression in the liver and small intestine and reduced Niemann Pick C1-like 1 gene expression in the small intestine, suggesting that K-877 administration induced HDL-C production in the liver and small intestine and reduced cholesterol absorption in the small intestine. In conclusion, K-877 administration had pronounced effects on the liver and small intestine in Ldlr-/- mice. K-877 is an attractive PPARα-modulating drug for treating hyperlipidemia that works equally well in both the liver and small intestine.

リンク情報
DOI
https://doi.org/10.1016/j.jphs.2017.02.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28366492
ID情報
  • DOI : 10.1016/j.jphs.2017.02.003
  • PubMed ID : 28366492

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