Effects of vitamin K2 on the expression of genes involved in bile acid synthesis and glucose homeostasis in mice with humanized PXR

Halima Sultana, Kimika Watanabe, Md Masud Rana, Rie Takashima, Ai Ohashi, Michio Komai, Hitoshi Shirakawa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Pregnane X receptor (PXR) is a nuclear receptor activated by various compounds, including prescribed drugs and dietary ingredients. Ligand-specific activation of PXR alters drug metabolism and affects many other physiological conditions. Species-specific ligand preference is a considerable challenge for studies of PXR function. To increase translational value of the results of mouse studies, humanized mouse model expressing human PXR (hPXR) has been developed. Menaquinone-4 (MK-4), one of vitamin K2 analogs prescribed in osteoporosis, is a PXR ligand. We hypothesized that MK-4 could modulate the physiological conditions endogenously influenced by PXR, including those that have not been yet properly elucidated. In the present study, we investigated the effects of a single oral treatment with MK-4 on hepatic gene expression in wild-type and hPXR mice by using quantitative RT-PCR and DNA microarray. MK-4 administration altered mRNA levels of genes involved in drug metabolism (Abca3, Cyp2s1, Sult1b1), bile acid synthesis (Cyp7a1, Cyp8b1), and energy homeostasis (Aldoc, Slc2a5). Similar mRNA changes of CYP7A1 and CYP8B1 were observed in human hepatocarcinoma HepG2 cells treated with MK-4. These results suggest that MK-4 may modulate bile acid synthesis. To our knowledge, this is the first report showing the effect of MK-4 in hPXR mice.

Original languageEnglish
Article number982
JournalNutrients
Volume10
Issue number8
DOIs
Publication statusPublished - 2018 Aug

Keywords

  • Bile homeostasis
  • Energy homeostasis
  • Gene expression
  • Menaquinone 4
  • PXR

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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