Format

Send to

Choose Destination
Nutrients. 2019 Jan 3;11(1). pii: E77. doi: 10.3390/nu11010077.

Beneficial Effects of Vitamin D Treatment in an Obese Mouse Model of Non-Alcoholic Steatohepatitis.

Author information

1
Division of Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany. jahn_d@ukw.de.
2
Division of Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany. dorbath_d@ukw.de.
3
Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany. stefan.kircher@uni-wuerzburg.de.
4
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria. anikan88@univie.ac.at.
5
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria. ina.bergheim@univie.ac.at.
6
NUTRIM School for Nutrition and Translational Research in Metabolism, Department of Surgery, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands. kaatje.lenaerts@maastrichtuniversity.nl.
7
Division of Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany. Hermanns_H@ukw.de.
8
Division of Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany. Geier_A2@ukw.de.
9
Division of Gastroenterology and Hepatology, University Hospital Zürich, 8091 Zürich, Switzerland. Geier_A2@ukw.de.

Abstract

Serum vitamin D levels negatively correlate with obesity and associated disorders such as non-alcoholic steatohepatitis (NASH). However, the mechanisms linking low vitamin D (VD) status to disease progression are not completely understood. In this study, we analyzed the effect of VD treatment on NASH in mice. C57BL6/J mice were fed a high-fat/high-sugar diet (HFSD) containing low amounts of VD for 16 weeks to induce obesity, NASH and liver fibrosis. The effects of preventive and interventional VD treatment were studied on the level of liver histology and hepatic/intestinal gene expression. Interestingly, preventive and to a lesser extent also interventional VD treatment resulted in improvements of liver histology. This included a significant decrease of steatosis, a trend towards lower non-alcoholic fatty liver disease (NAFLD) activity score and a slight non-significant decrease of fibrosis in the preventive treatment group. In line with these changes, preventive VD treatment reduced the hepatic expression of lipogenic, inflammatory and pro-fibrotic genes. Notably, these beneficial effects occurred in conjunction with a reduction of intestinal inflammation. Together, our observations suggest that timely initiation of VD supplementation (preventive vs. interventional) is a critical determinant of treatment outcome in NASH. In the applied animal model, the improvements of liver histology occurred in conjunction with reduced inflammation in the gut, suggesting a potential relevance of vitamin D as a therapeutic agent acting on the gut⁻liver axis.

KEYWORDS:

NAFLD; NASH; gut–liver axis; inflammation; intestine; obesity; vitamin D

PMID:
30609782
DOI:
10.3390/nu11010077
Free full text

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI)
Loading ...
Support Center