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Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism

International Journal of Obesity volume 35, pages 1019–1030 (2011)Cite this article

Subjects

Abstract

Introduction:

Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation.

Methods:

C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks.

Results:

Daidzein supplementation (⩾0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor β and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid β-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin.

Conclusions:

These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST, No. 2010-0020265) and by the Research Fund from the Research Institute of Human Ecology of Seoul National University.

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Authors and Affiliations

  1. Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea

    M-H Kim & Y-S Lee

  2. Research Institute of Human Ecology, Seoul National University, Seoul, Korea

    M-H Kim & Y-S Lee

  3. Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    J-S Park, J-W Jung & K-S Kang

  4. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    J-S Park, J-W Jung & K-S Kang

  5. Department of Food and Nutrition, Bucheon University, Bucheon, Korea

    K-W Byun

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Kim, MH., Park, JS., Jung, JW. et al. Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism. Int J Obes 35, 1019–1030 (2011). https://doi.org/10.1038/ijo.2010.256

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