Skip to main content
    • Aa
    • Aa
  • Access
  • Cited by 26
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Akhlaghi, Masoumeh 2016. Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids. Phytotherapy Research,

    Baali, Nacera Belloum, Zahia Baali, Samiya Chabi, Beatrice Pessemesse, Laurence Fouret, Gilles Ameddah, Souad Benayache, Fadila Benayache, Samir Feillet-Coudray, Christine Cabello, Gérard and Wrutniak-Cabello, Chantal 2016. Protective Activity of Total Polyphenols from Genista quadriflora Munby and Teucrium polium geyrii Maire in Acetaminophen-Induced Hepatotoxicity in Rats. Nutrients, Vol. 8, Issue. 4, p. 193.

    Domitrović, Robert and Potočnjak, Iva 2016. A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. Archives of Toxicology, Vol. 90, Issue. 1, p. 39.

    Martínez, Rosario Kapravelou, Garyfallia Porres, Jesús M. Melesio, Adela M. Heras, Leticia Cantarero, Samuel Gribble, Fiona M. Parker, Helen Aranda, Pilar and López-Jurado, María 2016. Medicago sativa L., a functional food to relieve hypertension and metabolic disorders in a spontaneously hypertensive rat model. Journal of Functional Foods, Vol. 26, p. 470.

    Rodriguez-Ramiro, I. Vauzour, D. and Minihane, A. M. 2016. Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms. Proceedings of the Nutrition Society, Vol. 75, Issue. 01, p. 47.

    Salomone, Federico Godos, Justyna and Zelber-Sagi, Shira 2016. Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives. Liver International, Vol. 36, Issue. 1, p. 5.

    Miller, Colette N. Yang, Jeong-Yeh Avra, Tucker Ambati, Suresh Della-Fera, Mary Anne Rayalam, Srujana and Baile, Clifton A. 2015. A dietary phytochemical blend prevents liver damage associated with adipose tissue mobilization in ovariectomized rats. Obesity, Vol. 23, Issue. 1, p. 112.

    Van De Wier, Bregje Koek, Ger H. Bast, Aalt and Haenen, Guido R.M.M. 2015. The Potential of Flavonoids in the Treatment of Non-alcoholic Fatty Liver Disease. Critical Reviews in Food Science and Nutrition, p. 00.

    CHEN, Tong ZHONG, Fo-Jin HONG, Ya-Min SU, Wei-Jiao ZHUANG, Li-Li and QIU, Long-Xin 2014. Effect of Trifolium pratense extract on methionine-choline-deficient diet-induced steatohepatitis in C57BL/6 mice. Chinese Journal of Natural Medicines, Vol. 12, Issue. 3, p. 194.

    Cheong, Sun Hee Furuhashi, Keisuke Ito, Katsuki Nagaoka, Masato Yonezawa, Takayuki Miura, Yutaka and Yagasaki, Kazumi 2014. Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice. The Journal of Nutritional Biochemistry, Vol. 25, Issue. 2, p. 136.

    Pan, Min-Hsiung Lai, Ching-Shu Tsai, Mei-Ling and Ho, Chi-Tang 2014. Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds. Molecular Nutrition & Food Research, Vol. 58, Issue. 1, p. 147.

    Xiao, Chao Wu Wood, Carla M. Weber, Dorcas Aziz, Syed A. Mehta, Rekha Griffin, Philip and Cockell, Kevin A. 2014. Dietary supplementation with soy isoflavones or replacement with soy proteins prevents hepatic lipid droplet accumulation and alters expression of genes involved in lipid metabolism in rats. Genes & Nutrition, Vol. 9, Issue. 1,

    Andersen, Charlotte Schjoldager, Janne G. Tortzen, Christian G. Vegge, Andreas Hufeldt, Majbritt R. Skaanild, Mette T. Vogensen, Finn K. Kristiansen, Karsten Hansen, Axel K. and Nielsen, John 2013. 2-Heptyl-Formononetin Increases Cholesterol and Induces Hepatic Steatosis in Mice. BioMed Research International, Vol. 2013, p. 1.

    Anhê, Fernando F. Desjardins, Yves Pilon, Geneviève Dudonné, Stéphanie Genovese, Maria Inés Lajolo, Franco M. and Marette, André 2013. Polyphenols and type 2 diabetes: A prospective review. PharmaNutrition, Vol. 1, Issue. 4, p. 105.

    Kurimoto, Yuta Shibayama, Yuki Inoue, Seiya Soga, Minoru Takikawa, Masahito Ito, Chiaki Nanba, Fumio Yoshida, Tadashi Yamashita, Yoko Ashida, Hitoshi and Tsuda, Takanori 2013. Black Soybean Seed Coat Extract Ameliorates Hyperglycemia and Insulin Sensitivity via the Activation of AMP-Activated Protein Kinase in Diabetic Mice. Journal of Agricultural and Food Chemistry, Vol. 61, Issue. 23, p. 5558.

    Leiherer, Andreas Mündlein, Axel and Drexel, Heinz 2013. Phytochemicals and their impact on adipose tissue inflammation and diabetes. Vascular Pharmacology, Vol. 58, Issue. 1-2, p. 3.

    Sharma, R. 2013. Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease.

    Sharma, R. 2013. Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease.

    Siriwardhana, Nalin Kalupahana, Nishan S. Cekanova, Maria LeMieux, Monique Greer, Betty and Moustaid-Moussa, Naima 2013. Modulation of adipose tissue inflammation by bioactive food compounds. The Journal of Nutritional Biochemistry, Vol. 24, Issue. 4, p. 613.

    Arunkumar, Elumalai and Anuradha, Carani Venkatraman 2012. Genistein promotes insulin action through adenosine monophosphate–activated protein kinase activation and p70 ribosomal protein S6 kinase 1 inhibition in the skeletal muscle of mice fed a high energy diet. Nutrition Research, Vol. 32, Issue. 8, p. 617.


The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease

  • Mi-Hyun Kim (a1), Kyung-Sun Kang (a2) (a3) and Yeon-Sook Lee (a1) (a4)
  • DOI:
  • Published online: 06 August 2010

Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with visceral adiposity, adipose tissue inflammation and a variety of adipocytokines. We reported previously that genistein inhibited NAFLD by enhancing fatty acid catabolism. However, this molecular approach focused on hepatic metabolism. Thus, we have attempted to determine whether this anti-steatotic effect of genistein is linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4 g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited increased visceral fat mass and elevated levels of serum and liver lipids, and developed NAFLD, unlike what was observed in mice fed on the NF diet. However, genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In the linear regression analysis, visceral fat (R 0·77) and TNFα (R 0·62) were strongly correlated with NAFLD among other NAFLD-related parameters. Genistein supplementation suppressed the hypertrophy of adipocytes via the up-regulation of genes involved in fatty acid β-oxidation, including PPARα, 5′-AMP-activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as through the down-regulation of genes associated with adipogenesis or lipogenesis, including liver X receptor-α, sterol-regulatory element-binding protein-1c, PPARγ, retinoid X receptor-α and acetyl CoA carboxylase 2. Moreover, genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and reduced a steatohepatitic TNFα. Collectively, these findings show that genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism and adipocytokines.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease
      Available formats
Corresponding author
*Corresponding authors: K.-S. Kang, fax:+82 2 876 7610, email; Y.-S. Lee, fax:+82 2 884 0305, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1BP Mulhall , JP Ong & ZM Younossi (2002) Non-alcoholic fatty liver disease: an overview. J Gastroenterol Hepatol 17, 11361143.

2G Targher , L Bertolini , L Scala , (2005) Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue. Diabet Med 22, 13541358.

3K Ikejima , K Okumura , K Kon , (2007) Role of adipocytokines in hepatic fibrogenesis. J Gastroenterol Hepatol 22, Suppl. 1, S87S92.

4 SP Weisberg , D McCann , M Desai , (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 17961808.

5 HH Zhang , M Halbleib , F Ahmad , (2002) Tumor necrosis factor-α stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51, 29292935.

6 D Cai , M Yuan , DF Frantz , (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11, 183190.

7AE Feldstein , NW Werneburg , A Canbay , (2004) Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway. Hepatology 40, 185194.

8W Huang , N Dedousis , A Bandi , (2006) Liver triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo. Endocrinology 147, 14801487.

9 M You , RV Considine , TC Leone , (2005) Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 42, 568577.

10 N Gallardo , E Bonzon-Kulichenko , T Fernandez-Agullo , (2007) Tissue-specific effects of central leptin on the expression of genes involved in lipid metabolism in liver and white adipose tissue. Endocrinology 148, 56045610.

11A Xu , Y Wang , H Keshaw , (2003) The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 112, 91100.

12 M Penza , C Montani , A Romani , (2006) Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. Endocrinology 147, 57405751.

13DM Tham , CD Gardner & WL Haskell (1998) Clinical review 97: potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83, 22232235.

14 YM Lee , JS Choi , MH Kim , (2006) Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets. Nutrition 22, 956964.

15 RS Surwit , MN Feinglos , J Rodin , (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 44, 645651.

16 RS Surwit , CM Kuhn , C Cochrane , (1988) Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37, 11631167.

19H Adlercreutz , H Markkanen & S Watanabe (1993) Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342, 12091210.

21KD Setchell , L Zimmer-Nechemias , J Cai , (1997) Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet 350, 2327.

23ZC Dang , V Audinot , SE Papapoulos , (2003) Peroxisome proliferator-activated receptor gamma (PPARgamma) as a molecular target for the soy phytoestrogen genistein. J Biol Chem 278, 962967.

24EG Bligh & WJ Dyer (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911917.

26 E Tsochatzis , GV Papatheodoridis , EK Manesis , (2007) Hepatic steatosis in genotype 4 chronic hepatitis C is mainly because of metabolic factors. Am J Gastroenterol 102, 634641.

28 RK Schindhelm , M Diamant , JM Dekker , (2006) Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. Diabetes Metab Res Rev 22, 437443.

29 L Abu-Elheiga , MM Matzuk , KA Abo-Hashema , (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291, 26132616.

30 JK Reddy & T Hashimoto (2001) Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor α: an adaptive metabolic system. Annu Rev Nutr 21, 193230.

31 A Naaz , M Zakroczymski , P Heine , (2002) Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor α (ERα): a potential role for estrogen receptor beta (ERbeta). Horm Metab Res 34, 758763.

32 T Szkudelski , L Nogowski , E Pruszynska-Oszmalek , (2005) Genistein restricts leptin secretion from rat adipocytes. J Steroid Biochem Mol Biol 96, 301307.

34AA Ali , MT Velasquez , CT Hansen , (2004) Effects of soybean isoflavones, probiotics, and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes. J Nutr Biochem 15, 583590.

35I Demonty , B Lamarche , Y Deshaies , (2002) Role of soy isoflavones in the hypotriglyceridemic effect of soy protein in the rat. J Nutr Biochem 13, 671677.

37 L Nogowski , P Mackowiak , K Kandulska , (1998) Genistein-induced changes in lipid metabolism of ovariectomized rats. Ann Nutr Metab 42, 360366.

38JG Fan , T Saibara , S Chitturi , (2007) What are the risk factors and settings for non-alcoholic fatty liver disease in Asia-Pacific? J Gastroenterol Hepatol 22, 794800.

39 JT Hwang , IJ Park , JI Shin , (2005) Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 338, 694699.

41 N Ruderman & M Prentki (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 3, 340351.

42 JJ Repa , G Liang , J Ou , (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14, 28192830.

43 S Le Lay , I Lefrere , C Trautwein , (2002) Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. J Biol Chem 277, 3562535634.

44 H Shimano , N Yahagi , M Amemiya-Kudo , (1999) Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem 274, 3583235839.

48 Y Zuo , L Qiang & SR Farmer (2006) Activation of CCAAT/enhancer-binding protein (C/EBP) α expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp α gene promoter. J Biol Chem 281, 79607967.

49 AW Harmon , YM Patel & JB Harp (2002) Genistein inhibits CCAAT/enhancer-binding protein beta (C/EBPbeta) activity and 3T3-L1 adipogenesis by increasing C/EBP homologous protein expression. Biochem J 367, 203208.

50A Chawla , JJ Repa , RM Evans , (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294, 18661870.

51 M Higuchi , RJ Proske & ET Yeh (1998) Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene 17, 25152524.

52 N Ouchi , S Kihara , Y Arita , (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102, 12961301.

54M Yalniz , IH Bahcecioglu , N Kuzu , (2007) Preventive role of genistein in an experimental non-alcoholic steatohepatitis model. J Gastroenterol Hepatol 22, 20092014.

55 R Hasumuma , K Kawaguchi , S Kikuchi , (2007) Effects of isoflavones and soybeans fermented with Bacillus subtilis on lipopolysaccharide-induced production of tumor necrosis factor-α and fibrinolysis in vivo. Immunopharmacol Immunotoxicol 29, 323333.

56WM Mueller , FM Gregoire , KL Stanhope , (1998) Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology 139, 551558.

57 JR Levy & W Stevens (2001) The effects of insulin, glucose, and pyruvate on the kinetics of leptin secretion. Endocrinology 142, 35583562.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Kim supplementary material
Table 1.doc

 Unknown (49 KB)
49 KB
Supplementary Materials

Kim supplementary material
Table 2.doc

 Unknown (45 KB)
45 KB