Protective Effects of White Button Mushroom (Agaricus bisporus) against Hepatic Steatosis in Ovariectomized Mice as a Model of Postmenopausal Women

Noriko Kanaya,Zheng Liu,Charles Wang,Makoto Kubo,Peiguo Chu,Yate-Ching Yuan, Shiuan Chen,Franky L Chan

doi:10.1371/journal.pone.0026654

Abstract

Nonalcoholic fatty liver disease (NAFLD) includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Estrogen provides a protective effect on the development of NAFLD in women. Therefore, postmenopausal women have a higher risk of developing NAFLD. Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis). Currently, there is no specific drug to prevent/treat these liver diseases. In this study, we found that white button mushroom (WBM), Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX) mice (a model of postmenopausal women). OVX mice were fed a high fat diet supplemented with WBM powder. We found that dietary WBM intake significantly lowered liver weight and hepatic injury markers in OVX mice. Pathological examination of liver tissue showed less fat accumulation in the livers of mice on WBM diet; moreover, these animals had improved glucose clearance ability. Microarray analysis revealed that genes related to the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6), were down-regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR) signaling and its downstream transcriptional factor SREBP1c. These results suggest that WBM is protective against hepatic steatosis and NAFLD in OVX mice as a model for postmenopausal women.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in adults in developed countries [1]
No significant differences in body weight were observed between the control group fed the high fat diet (HFD) and the group fed with HFD+white button mushroom (WBM) in both the sham and the OVX groups (Figure 1A and 1B)
No significant differences in uterine weight were observed between HFD and high fat diet with WBM powder (HFD+WBM) in both groups (Figure 1E)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in adults in developed countries [1]. It is characterized by excessive hepatic lipid accumulation and is not related to alcohol use. NAFLD includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Cirrhosis is a risk factor for the development of portal hypertension, hepatocellular carcinoma and liver failure [1]. It has been suggested that estrogen provides a protective effect on the development of NAFLD in women [3]. Postmenopausal women have a higher risk of developing NAFLD due to a lower level of circulating estrogen [3]. Dietary and lifestyle guidelines to reduce overall body weight may help avoid NAFLD, there are no specific drugs to treat this liver disease [5]

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