A Lipid-Based Nanocarrier Containing Active Vitamin D3 Ameliorates NASH in Mice via Direct and Intestine-Mediated Effects on Liver Inflammation

Yunmei Mu, Jinting Li, Jeong Hun Kang, Hinako Eto, Khadijah Zai, Akihiro Kishimura, Fuminori Hyodo, Takeshi Mori, Yoshiki Katayama

Research output: Contribution to journalArticlepeer-review

Abstract

The gut-liver axis may be involved in non-alcoholic steatohepatitis (NASH) progression. Pathogen-associated molecular patterns leak through the intestinal barrier to the liver via the portal vein to contribute to NASH development. Active vitamin D3 (1,25(OH)2D3) is a potential therapeutic agent to enhance the intestinal barrier. Active vitamin D3 also suppresses inflammation and fibrosis in the liver. However, the adverse effects of active vitamin D3 such as hypercalcemia limit its clinical use. We created a nano-structured lipid carrier (NLC) containing active vitamin D3 to deliver active vitamin D3 to the intestine and liver to elicit NASH treatment. We found a suppressive effect of the NLC on the lipopolysaccharide-induced increase in permeability of an epithelial layer in vitro. Using mice in which NASH was induced by a methionine and choline-deficient diet, we discovered that oral application of the NLC ameliorated the permeability increase in the intestinal barrier and attenuated steatosis, inflammation and fibrosis in liver at a safe dose of active vitamin D3 at which the free form of active vitamin D3 did not show a therapeutic effect. These data suggest that the NLC is a novel therapeutic agent for NASH.

Original languageEnglish
Pages (from-to)1413-1420
Number of pages8
JournalBiological & pharmaceutical bulletin
Volume43
Issue number9
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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