Vitamin D Receptor Modulates Intestinal Lipid Metabolism, Adipose Tissue Inflammation and Hepatic Steatosis in Diet-induced Obese Mice

Background:

Vitamin D effects are mediated via the nuclear Vitamin D Receptor (VDR). Vitamin D insufficiency is frequently observed in obesity and NAFLD. The contribution of VDR to the pathomechanisms of these entities is, however, incompletely understood. We investigated the impact of global and intestine-specific Vitamin D signaling on the development of obesity and NAFLD in genetically-modified mice.

Methods:

Diet-induced obesity, adipose tissue (AT) inflammation and early NAFLD were analyzed in three groups of mice: Heterozygous mice served as controls. “Whole-body” Vdr-KO mice served as a model to study global effects of Vitamin D signaling. Vdr-KOhTg mice expressing an intestine-specific human VDR in the Vdr-KO background allowed studying intestinal Vdr effects. Phenotyping was performed by histological examination, gene expression analysis and measurement of serum/fecal parameters.

Results:

Vdr-KO mice were protected from HFD-induced obesity, AT inflammation and hepatic steatosis when compared to heterozygous controls. Interestingly, this protection was partly reversed in Vdr-KOhTg animals which showed increased weight gain, AT inflammation and hepatic steatosis compared to Vdr-KOs. To investigate the underlying mechanism, intestinal mRNA expression was analyzed with regard to genes involved in lipid metabolism. Here, changes in certain factors with known impact on peripheral LPL activity and/or intestinal lipid absorption could be detected. In line with this, changes in serum TGs and fecal fat content were observable among the different genotypes.

Conclusion:

These data point to a role of intestinal Vdr as a novel regulator of intestinal/systemic lipid metabolism modulating obesity and associated inflammatory changes in AT and liver.

Corresponding author: Jahn, Daniel

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