The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease.
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.
Kim
Mi-Hyun
MH
Department of Food and Nutrition, College of Human Ecology, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea.
Kang
Kyung-Sun
KS
Lee
Yeon-Sook
YS
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D004041:Dietary Fats / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D006984:Hypertrophy; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D016014:Linear Models; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D013025:Glycine max / Q000737:chemistry; D048069:Tumor Necrosis Factors / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D004041:Dietary Fats; D000960:Hypolipidemic Agents; D048789:Phytoestrogens; D010936:Plant Extracts; D048069:Tumor Necrosis Factors; D019833:Genistein