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