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

• Published in: International Journal of Obesity Vol. 35; no. 8; pp. 1019 - 1030
• Main Authors: Kim, M.H, Park, J.S, Jung, J.W, Byun, K.W, Kang, K.S, Lee, Y.S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.08.2011; Nature Publishing Group UK
• Subjects: 631/443/319; 631/80/86/2367; 692/699/1503/1607/2750; 692/700/459/1994; adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipokines - metabolism; adiponectin; Adipose Tissue - drug effects; Adipose Tissue - metabolism; adiposity; Animals; beta oxidation; binding proteins; Biological and medical sciences; Blood; blood glucose; Body Weight; daidzein; Diet; Energy; enzymes; Epidemiology; Fatty acids; Fatty liver; Fatty Liver - drug therapy; Fatty Liver - metabolism; Fatty Liver - prevention & control; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene Expression Profiling; gene expression regulation; genes; Genetic aspects; ghrelin; Health aspects; Health Promotion and Disease Prevention; homeostasis; insulin; Insulin - metabolism; Insulin Resistance; Internal Medicine; Isoflavones; Isoflavones - pharmacology; leptin; lipogenesis; Lipogenesis - drug effects; Liver; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Medicine; Medicine & Public Health; messenger RNA; Metabolic Diseases; Metabolism; Mice; Mice, Inbred C57BL; microarray technology; Non-alcoholic Fatty Liver Disease; Nutrition; Obesity; original-article; Other diseases. Semiology; Oxidation; Phytoestrogens - pharmacology; Prevention and actions; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reverse Transcriptase Polymerase Chain Reaction; tumor necrosis factor-alpha; Tumor necrosis factor-TNF; Veterinary colleges; South Korea; daidzein; hepatic; lipogenesis; non-alcoholic fatty liver disease; insulin signaling; adipocyte metabolism; Adipocyte; Pancreatic hormone; Alcoholic hepatitis; Liver; Hepatic disease; non-alcoholic tatty liver disease; Prevention; Signal transduction; Supplementation; Lipogenesis; Nutritional status; Obesity; Nutrition; Digestive system; Nutrition disorder; Metabolic diseases; Metabolism; hepatic de novo lipogenesis; Insulin; De novo; Gene expression profile; Non alcoholic steatohepatitis; Digestive diseases; Daidzein
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2010.256

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 beta 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 beta-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 alpha 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.