@article{aa879facea684e3e8b4681dc99d1e1bb,
title = "Beneficial Effects of Vitamin D Treatment in an Obese Mouse Model of Non-Alcoholic Steatohepatitis",
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 = "vitamin D, obesity, NAFLD, NASH, inflammation, intestine, gut-liver axis, FATTY LIVER-DISEASE, DIET-INDUCED OBESITY, D DEFICIENCY, D-RECEPTOR, INSULIN SENSITIVITY, METABOLIC SYNDROME, IMMUNE-SYSTEM, RISK-FACTORS, BILE-ACIDS, SUPPLEMENTATION",
author = "Daniel Jahn and Donata Dorbath and Stefan Kircher and Anika Nier and Ina Bergheim and Kaatje Lenaerts and Hermanns, {Heike M.} and Andreas Geier",
note = "Funding Information: Conflicts of Interest: DJ received travel grants from Alexion and Falk. HMH consulted for GlaxoSmithKline and received travel grants from Falk. AG advises for AbbVie, Alexion, BMS, Gilead, Intercept, Novartis, and Sequana, is on the speakers{\textquoteright} bureau for AbbVie, Alexion, BMS, Falk, Gilead, Intercept, Novartis and Sequana, received research grants from Intercept and Novartis, and received material resources from Burgerstein Vitamine (study medication for SASL34). IB received funding from Yakult Ltd. The other authors declare no conflict of interests. The funders of this study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. Funding Information: Acknowledgments: This work was supported by grants of the Schweizerischer Nationalfonds (SNF) and the Else Kr{\"o}ner-Fresenius-Stiftung (EKFS) to A.G. D.J. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of W{\"u}rzburg. This publication was funded by the German Research Foundation (DFG) and the University of W{\"u}rzburg in the funding program Open Access Publishing. Parts of this study have been published as conference abstracts at the International Liver Congress (EASL) and the Annual Meeting of the German Association for the Study of the Liver (GASL). Funding Information: This research was funded by the Schweizerischer Nationalfonds zur F{\"o}rderung der Wissenschaftlichen Forschung (grant number 310030_135548) and the Else Kr{\"o}ner-Fresenius-Stiftung (grant number 2014_A67). The APC was funded by the German Research Foundation and the University of W{\"u}rzburg in the funding program Open Access Publishing. Acknowledgments: This work was supported by grants of the Schweizerischer Nationalfonds (SNF) and the Else Kr{\"o}ner-Fresenius-Stiftung (EKFS) to A.G. D.J. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of W{\"u}rzburg. This publication was funded by the German Research Foundation (DFG) and the University of W{\"u}rzburg in the funding program Open Access Publishing. Parts of this study have been published as conference abstracts at the International Liver Congress (EASL) and the Annual Meeting of the German Association for the Study of the Liver (GASL). Funding Information: Funding: This research was funded by the Schweizerischer Nationalfonds zur F{\"o}rderung der Wissenschaftlichen Forschung (grant number 310030_135548) and the Else Kr{\"o}ner-Fresenius-Stiftung (grant number 2014_A67). The APC was funded by the German Research Foundation and the University of W{\"u}rzburg in the funding program Open Access Publishing. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = jan,
doi = "10.3390/nu11010077",
language = "English",
volume = "11",
pages = "1--14",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",
}