A role of 1,25(OH)2D3 supplementation in rats with nonalcoholic steatohepatitis induced by choline-deficient diet
Introduction
Nonalcoholic steatohepatitis (NASH) is a very common metabolic liver disorder. In laboratory animals, a choline-deficient (CD) diet may induce a comprehensive histological and dysmetabolic phenotype resembling human NASH [1], [2]. This phenotype is characterized by fatty liver, inflammation, fibrosis, cirrhosis, and even hepatocellular carcinoma [3].
Vitamin D3 (VD3) has been shown to act as an immunomodulatory, antioxidant, anti-inflammatory, and anti-apoptotic compound in rodents [4], [5]. It is unclear if VD3 supplementation can be used to protect against CD-induced NASH. Recent findings on the effect of phototherapy and orally administrated 1α(OH)D3 [5] suggest that vitamin D (VD) supplements may slow down NASH progression in rats via reducing the production of pro-inflammatory cytokines and inducing anti-apoptotic processes. In this study, an iron supplement was included in the CD diets of the NASH model animals, and therefore an antagonistic effect of VD3 supplementation on the promotion of oxidative stress and apoptosis caused by the iron overload cannot be ruled out.
We recently reported that intraperitoneal (IP) injections of 1,25(OH)2D3 (1,25-VD3) in rats kept on a CD diet with iron at a standard level ameliorate the progression of NASH, leading to improvement in the levels of liver injury and inflammation [6].
In the present study, we further studied the roles of 1,25-VD3 supplementation in rat NASH models. We investigated the effects of different dosages of 1,25-VD3 on NASH, and we analyzed the association of such effects with the serum level of 25-(OH)D3 and hepatic expression of vitamin D receptors (VDR).
Section snippets
Animals and experimental treatments
All experimental procedures on animals were approved by the Ethics Committee of Yanbian University. The Ethical Guidelines of the China Association of Laboratory Animal Care were strictly followed in the experiments.
Six-week-old male Wistar rats (150–180 g) were obtained from the Yisi Experimental Animal Technology Company (Changchun, China). After a 1-week acclimation period, the animals were randomly assigned into three groups: a control group (CG, n = 5) with adequate level of dietary
Effects of 1,25-VD3 on body weight, liver weight, and liver index
After 12 weeks on a CD diet, the CDG rats showed an increase in the liver weight as compared with the CG (15.80 ± 0.96 g vs. 12.60 ± 0.18 g, respectively, p < 0.05) with no significant difference in body weight (454.58 ± 25.16 g vs. 464.76 ± 2.88 g, respectively, p > 0.05). In comparison with the CDG, the CDVDG showed no significant decrease in either body weight or liver weight.
The liver index was calculated as liver weight divided by body weight. The liver index in the CDG was significantly
Discussion
In this study, we demonstrated that 1,25-VD3 supplementation influences the level of liver injury and development and progression of NASH induced by a CD diet in rats. Supplementation led to elevation of serum level of 25-(OH)D3 and hepatic expression of VDR.
Hepatic TG and FFA are major lipids in the liver [12], [13]. In support of our pilot study [6], it has been reported that phototherapy may reduce the TG accumulation in liver by enhancing TG release into the bloodstream [5]. Interestingly,
Acknowledgments
This work was supported by grants from the Yanbian University Science and Technology of China. Hongmei Han was also supported by the PhD program of the Medical University of Yanbian (No.601010001).
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