Division of Tumor Cell Biology, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
PLoS One. 2011;6(10):e26654. doi: 10.1371/journal.pone.0026654. Epub 2011 Oct 25.
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.
非酒精性脂肪性肝病（NAFLD）包括从肝脂肪变性到非酒精性脂肪性肝炎（NASH）、纤维化和肝硬化等各种肝病理变化。雌激素对女性 NAFLD 的发展具有保护作用。因此，绝经后妇女发生 NAFLD 的风险更高。肝脂肪变性是脂肪肝的早期阶段。脂肪变性可发展为侵袭性阶段（非酒精性脂肪性肝炎、纤维化和肝硬化）。目前，尚无专门用于预防/治疗这些肝病的药物。在这项研究中，我们发现白蘑菇（WBM），双孢蘑菇，对去卵巢（OVX）小鼠（绝经后妇女模型）的肝脂肪变性具有保护作用。OVX 小鼠喂食高脂肪饮食，补充 WBM 粉末。我们发现，饮食中摄入 WBM 可显著降低 OVX 小鼠的肝重和肝损伤标志物。肝组织病理学检查显示，WBM 饮食组小鼠肝脏脂肪堆积减少；此外，这些动物的葡萄糖清除能力得到改善。微阵列分析显示，与脂肪酸生物合成途径相关的基因，特别是脂肪酸合成酶（Fas）和脂肪酸延长酶 6（Elovl6）的基因，在蘑菇喂养的小鼠肝脏中下调。使用 HepG2 细胞系的体外机制研究表明，WBM 提取物下调 FAS 和 ELOVL6 的表达是通过抑制肝 X 受体（LXR）信号及其下游转录因子 SREBP1c 实现的。这些结果表明，WBM 可预防 OVX 小鼠（作为绝经后妇女的模型）的肝脂肪变性和 NAFLD。
