British Journal of Nutrition

Full Papers

Nutritional Endocrinology

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 Kima1, Kyung-Sun Kanga2a3 c1 and Yeon-Sook Leea1a4 c1

a1 Department of Food and Nutrition, College of Human Ecology, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea

a2 Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea

a3 Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea

a4 Research Institute of Human Ecology, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea

Abstract

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.

(Received December 02 2009)

(Revised April 19 2010)

(Accepted April 29 2010)

(Online publication August 06 2010)

Correspondence:

c1 Corresponding authors: K.-S. Kang, fax:+82 2 876 7610, email kangpub@snu.ac.kr; Y.-S. Lee, fax:+82 2 884 0305, email lysook@snu.ac.kr

Footnotes

Abbreviations: ACC, acetyl CoA carboxylase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BW, body weight; C/EBP, CCAAT/enhancer-binding proteins; ER, oestrogen receptor; HF, high fat; LXR, liver X receptor; NAFLD, non-alcoholic fatty liver disease; NF, normal fat; RXR, retinoid X receptor; SREBP, sterol-regulatory element-binding protein

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