Z Gastroenterol 2014; 52 - G3
DOI: 10.1055/s-0034-1386663

Vitamin D3 acts on the gut-liver-adipose tissue axis to modulate obesity-associated inflammatory changes in diet-induced obese mice

D Jahn 1, L Gildein 1, J Fleet 2, J Schmitt 1, H Hermanns 1, A Geier 1
  • 1University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany
  • 2Department of Nutrition Science, Purdue University, West Lafayette, USA

Background: Obesity and associated metabolic complications are increasing problems in industrialized countries. Serum 25-OH Vitamin D3 (VD3) levels negatively correlate with BMI, insulin resistance and NAFLD in humans.

Methods: To explore the relevance of VD3 for obesity and NAFLD, C57BL/6 mice were fed high-fat diets (HFD) with different levels of VD3. Gene expression in liver and adipose tissue (AT) was analysed by qPCR. Serum parameters were determined by ELISA. Tissue-specific effects of VD3 were investigated in Vitamin D receptor (VDR)-deficient mice (VDR-KO) and VDR-KO mice with an intestine-specific VDR transgene (VDR-KO hTg).

Results: High dietary VD3 enhanced HFD-induced weight gain and increased fat mass. This was associated with up-regulation of chemokine signalling in AT and a shift towards pro-inflammatory M1-macrophages. In line, fasting glucose and serum insulin were elevated in HFD mice with high VD3 intake. These AT-specific changes coincided with trends towards increased immune activation and ER stress in the liver. Analysis of VDR-KO hTg mice revealed increased body weight and fat mass compared to VDR-KO in response to HFD-feeding.

Conclusions: These findings highlight the pathophysiological importance of the gut-liver-adipose tissue axis for NAFLD and obesity. Moreover, our data reveal a potential adipogenic effect of VD3 in the applied HFD-model and point to an unanticipated role of intestinal VDR in the regulation of body weight and lipid metabolism.