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. 2017 Nov 28;17(1):130.
doi: 10.1186/s12876-017-0688-4.

Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin D-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift

A Drori  1 , D Rotnemer-Golinkin  1 , S Avni  2 , A Drori  3 , O Danay  2 , D Levanon  2 , J Tam  3 , L Zolotarev  1 , Y Ilan  4
Affiliations

Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin D-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift

A Drori et al. BMC Gastroenterol. .

Abstract

Background: Hypovitaminosis D is associated with many features of the metabolic syndrome, including non-alcoholic fatty liver disease. Vitamin D-enriched mushrooms extracts exert a synergistic anti-inflammatory effect. The aim of the present study is to determine the immunomodulatory effect of oral administration of vitamin D-enriched mushrooms extracts on high-fat diet (HFD) animal model of non-alcoholic steatohepatitis (NASH).

Methods: C57BL/6 mice on HFD were orally administered with vitamin D supplement, Lentinula edodes (LE) mushrooms extract, or vitamin D-enriched mushrooms extract for 25 weeks. Mice were studied for the effect of the treatment on the immune system, liver functions and histology, insulin resistance and lipid profile.

Results: Treatment with vitamin D-enriched LE extracts was associated with significant attenuation of the rate of total body fat accumulation, along with a decrease in hepatic fat content as measured by an EchoMRI. Significant alleviation of liver damage manifested by a marked decrease in ALT, and AST serum levels (from 900 and 1021 U/L in the control group to 313 and 340; 294 and 292; and 366 and 321 U/L for ALT and AST, in Vit D, LE and LE + Vit D treated groups, respectively). A corresponding effect on hepatocyte ballooning were also noted. A significant decrease in serum triglycerides (from 103 to 75, 69 and 72 mg/dL), total cholesterol (from 267 to 160, 157 and 184 mg/dL), and LDL cholesterol (from 193 mg/dL to 133, 115 and 124 mg/dL) along with an increase in the HDL/LDL ratio, and improved glucose levels were documented. These beneficial effects were associated with a systemic immunomodulatory effect associated with an increased CD4/CD8 lymphocyte ratio (from 1.38 in the control group to 1.69, 1.71 and 1.63), and a pro- to an anti-inflammatory cytokine shift.

Conclusions: Oral administration of vitamin-D enriched mushrooms extracts exerts an immune modulatory hepato-protective effect in NASH model.

Keywords: Lentinula edodes; NASH; Shiitake; Vitamin D.

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Conflict of interest statement

Ethics approval and consent to participate

Experiments were carried out on animals according to the guidelines of the Hebrew University-Hadassah Institutional Committee for the Care and Use of Laboratory Animals with the committee’s approval.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Effect of oral administration of vitamin D-enriched mushrooms on liver damage. Trend-lines representing the rate of total body fat (%) accumulation, calculated as the slope of the linear line throughout the study (a). Effect of treatment on total body fat (%) as measured by EchoMRI at the end of the experiment (b). Data represent mean +/− SE from N = 4–6 mice per group. p value (by Kruskal-Wallis test) < 0.05 for Total body fat (%). * - p value <0.05 (by Mann-Whitney test)
Fig. 2
Fig. 2
Effect of oral administration of vitamin D-enriched mushrooms on serum lipids & glucose levels. Effect of treatment on triglycerides (TG), total cholesterol (T-Chol), high-density lipoproteins (HDL), low-density lipoproteins (LDL-c, calculated) and HDL/LDL ratio (a-e). Effect of treatment on serum glucose levels (f). Data represent mean +/− SE from N = 4–6 mice per group. p value (by Kruskal-Wallis test) < 0.05 for all measured parameters. * - p value <0.05 (by Mann-Whitney test)
Fig. 3
Fig. 3
Effect of oral administration of vitamin D-enriched mushrooms on liver damage. Effect of treatment on serum liver enzymes levels: ALT, AST and GGT (a). Effect of treatment on hepatic fat content (%) as measured by EchoMRI (b). Effect of treatment on NAS score: ballooning, inflammation, Steatosis and overall NAS score were calculated for mice in all groups (c-f). Effect of treatment on liver histology: Representative slides from all groups are shown (H&E, ×10) (g). Data represent mean +/− SE from N = 4–6 mice per group. p value (by Kruskal-Wallis test) < 0.05 for Liver fat (%) week 25 and hepatocytes ballooning. * - p value <0.05 (by Mann-Whitney test)
Fig. 4
Fig. 4
Effect of oral administration of vitamin D-enriched mushrooms on the immune system. Serum levels of TNFα, IL-1α, IL-1β, TGFβ, IL-6 and IL-10 were measured by ELISA at the end of the study (a-f). FACS analysis was performed on lymphocytes isolated from spleens. Effect of treatment on the CD4/CD8 lymphocyte ratio (g). Data represent mean +/− SE from N = 4–6 mice per group. p value (by Kruskal-Wallis test) < 0.05 for TNFα, IL-1α, IL-1β and IL-6. * - p value <0.05 (by Mann-Whitney test)
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