title: Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.
authors.forename: M-H
authors.initials: MH
authors.lastname: Kim
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
authors.forename: J-W
authors.initials: JW
authors.lastname: Jung
authors.forename: K-W
authors.initials: KW
authors.lastname: Byun
authors.forename: K-S
authors.initials: KS
authors.lastname: Kang
authors.forename: Y-S
authors.initials: YS
authors.lastname: Lee
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004032:Diet; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D020869:Gene Expression Profiling; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007529:Isoflavones / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D048789:Phytoestrogens / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054392:Adipokines; D007328:Insulin; D007529:Isoflavones; D048789:Phytoestrogens; C004742:daidzein