Vitamin D3 in ameliorating diabetes-induced liver failure associated with impaired VDR signaling and inflammation

D. Labudzynskyi (1, 2) , I. Shymanskyy (1) , Lauriane Bonnet (3) , Jean-Francois Landrier (3) , M. Veliky (1)

1 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine
2 Biomed Ctr
3 NORT - Nutrition, obésité et risque thrombotique

Introduction: Vitamin D3 (D3) has recently been recognized as a potent immunomodulator which acts through regulation of gene expression involved in immunity response thus affecting various inflammatory and autoimmune diseases. The study was aimed at investigating hepatoprotective role of D3 in VDR-mediated regulation of pro- inflammatory factors in diabetic liver. Materials and Methods: Type 1 diabetes was induced in male C57BL/J6 mice by i.p. injection of high-dose STZ (150mg/kg b.w.). After 2 weeks of STZ-induced diabetes animals were treated with/without D3 (15 IU/mouse per os) for 8 weeks. Blood serum 25OHD3 was assessed by ELISA. Rel-A, VPF, iNOS and VDR expression was measured by qRT-PCR and/or Western-blot. Results and Discussion: Diabetes caused two-fold reduction of serum 25OHD3 level, indicative of D3 deficiency. Significant alterations in D3-endocrine system were found as is evident from reduced expression of CYP27A1, CYP2R1, VDBP and VDR at transcriptional and translational levels. These changes were accompanied by a marked increase in mRNA and protein levels of inflammation markers Rel-A, VPF and iNOS in hepatic tissue of diabetic mice. Diabetes also led to structural lesions in liver tissue. Complete restoration of 25OHD3 content and partial normalization of liver tissue structure were achieved after D3 treatment. D3 administration partially normalized expression of cytochromes involved in D3 metabolism and hepatic pro- inflammatory factors. D3 treatment prevented overexpression of Rel-A and phosphorylated p65/Rel-A translocation to hepatocellular nuclei that is most likely mediated through 1,25(OH)2D3 and VDR. Conclusion: Study confirmed that diabetes-induced liver abnormalities are associated with chronic inflammation that can be linked to impaired D3 metabolism and deficiency. Our findings demonstrate protective VDR-mediated effect of vitamin D3 against diabetes-induced liver injury.

Mots clés: immunomodulator; vitamin d3; receiver; inflammatory disease; liver insufficiency

Mots clés: immunomodulateur; vitamine d3; récepteur; maladie inflammatoire; maladie autoimmune; diabète de type 1; maladie hépatique; insuffisance hépatique

Domaines: Immunologie

D. Labudzynskyi, I. Shymanskyy, Lauriane Bonnet, Jean-Francois Landrier, M. Veliky. Vitamin D3 in ameliorating diabetes-induced liver failure associated with impaired VDR signaling and inflammation. Symposium on Theory of Modeling and Simulation (DEVS/TMS 2011), Sep 2016, Kusadasi, Turkey. pp.1. ⟨hal-01594624⟩