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Calcium and vitamin D3 combinations improve fatty liver disease through AMPK-independent mechanisms

European Journal of Nutrition volume 57, pages 731–740 (2018)Cite this article

Abstract

Purpose

Some research findings suggest that calcium plus vitamin D (VitD) might have a preventive effect on nonalcoholic fatty liver disease development. Moreover, contradictory evidence also exists regarding calcium and VitD deficient diets. This study aimed to evaluate the effect of four different dietary calcium and VitD3 (cholecalciferol) levels on the development of high-fat, high-fructose (HFHFr) diet-induced nonalcoholic fatty liver disease and AMP-activated protein kinase (AMPK) phosphorylation.

Methods

Thirty male Wistar rats were fed with normal or HFHFr diet containing low calcium (0.2%) and VitD3 (250 IU/kg) (LCD), normal calcium (0.5%) and VtD3 (1000 IU/kg) (CN), high calcium (1.2%) and VitD3 (4000 IU/kg) (HCD) or very high amount of calcium (2.4%) and VitD3 (10,000 IU/kg) (VHCD). After 60 days, anthropometric, metabolic and hepatic parameters were evaluated. The effect of the experimental diets on liver AMPK phosphorylation was also investigated.

Results

Rats fed on high calcium plus VitD3 diets, especially VHCD, demonstrated lower adiposity, serum liver enzymes, hepatic lipid accumulation and steatosis. The LCD diet also decreased hepatic lipid content and fatty changes. No evidence indicating the involvement of AMPK in the observed associations was found (P value = 0.51).

Conclusions

The results showed high calcium plus VitD3 intakes considerably prevent biochemical and hepatic changes induced by HFHFr diet, probably via an insulin and AMPK-independent pathway. A low intake of these two nutrients was also linked with a significant decrease in HFHFr diet-induced hepatic steatosis.

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Acknowledgements

This article is extracted from a master’s thesis in Nutrition and supported by Urmia University of Medical Sciences. The authors would like to express their gratitude toward Dr. Amir Abbas Farshid and Dr. Ali Asghar Tehrani for conducting the pathological assessments. The authors would also like to thank the Pharma chemie and Daana Pharmaceutical Companies and Beyza 21 Feed Mill Company.

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Authors and Affiliations

  1. Student Research Committee, Department of Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Sara Shojaei Zarghani

  2. Cellular and Molecular Research Center, Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

    Hamid Soraya

  3. Department of Nutrition, Food and Beverages Safety Research Center, Faculty of Medicine, Urmia University of Medical Sciences, PO Box: 5756115111, Urmia, Iran

    Mohammad Alizadeh

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  1. Sara Shojaei Zarghani
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Correspondence to Mohammad Alizadeh.

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All animal protocols were approved by the Ethics Committee of Urmia Medical Sciences University (ir.umsu.rec.1393.281).

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Shojaei Zarghani, S., Soraya, H. & Alizadeh, M. Calcium and vitamin D3 combinations improve fatty liver disease through AMPK-independent mechanisms. Eur J Nutr 57, 731–740 (2018). https://doi.org/10.1007/s00394-016-1360-4

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Keywords

  • Nonalcoholic fatty liver disease
  • Calcium
  • Vitamin D3
  • AMP-activated protein kinase