Genistein activated SIRT1-AMPK signaling pathway mediated by ERβ-FOXO1-Nampt to reduce fat accumulation in chicken hepatocytes
Genistein activated SIRT1-AMPK signaling pathway mediated by ERβ-FOXO1-Nampt to reduce fat accumulation in chicken hepatocytes
复制标题
金雀异黄素激活ERβ-FOXO1-Nampt介导的SIRT1-AMPK信号通路减少鸡肝细胞脂肪堆积
DOI：
10.1016/j.lfs.2022.121259
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发表时间：
2022-12-05
期刊：
影响因子：
6.1
通讯作者：
Ma, Haitian
中科院分区：
文献类型：
--
作者：
Jiang, Zhihao;Wang, Huihui;Ma, Haitian
肉鸡脂肪堆积过多将严重威胁家禽养殖业。导致饲料转化率低，肉质变差。更糟糕的是，由于摄入高脂鸡肉产品，它损害了消费者的健康。含有生物活性成分的膳食补充剂被认为是解决这一问题的有效方法。染料木素是大豆中主要的植物雌激素。其降脂作用已有报道，但其分子机制尚不清楚。本研究发现金雀异黄素通过调节脂类代谢相关因子在鸡肝细胞中的表达，减少了脂滴的蓄积。研究表明，金雀异黄素可显著增加p-AMPK和Sirtuin1蛋白的表达。SIRT1抑制剂可完全阻断金雀异黄素减少脂滴蓄积和上调p-AMPK蛋白水平的作用。这些结果表明，激活AMPK需要SIRT1。此外，金雀异黄素可显著上调AMPK抑制剂处理后SIRT1蛋白水平。我们证实雌激素受体β-Forkhead box O1-烟酰胺磷酸核糖转移酶(ER-β-FOXO1-NAMPT)信号通路的激活上调了肝细胞内NAD(+)的浓度，最终激活了SIRT1。综上所述，我们证明金雀异黄素通过激活SIRT1-AMPK来抑制鸡肝细胞内脂滴的聚集。SIRT1-AMPK信号通路由ERβ-FOXO1-NAMPT介导。这些发现加深了我们对金雀异黄素降脂机理的理解，并为其作为一种营养补充剂预防动物乃至人类的过度脂肪沉积和脂代谢相关疾病提供了令人信服的证据。
Excessive fat accumulation in broiler chickens would seriously threaten the poultry industry. It leads to lower feed conversion rate and worse meat quality. Even worse, it harms the consumers' health due to the intake of high-fat chicken products. Dietary supplements with bioactive ingredients have been considered an effective way to solve this problem. Genistein is the primary phytoestrogen in soybean. Its fat-reduction effect has been reported, but the molecular mechanism is unclear. The present study found that genistein reduced lipid droplets accumulation by regulating lipid metabolism-related factors expression in chicken hepatocytes. The research showed that genistein significantly increased phosphor (p)-AMP-activated protein kinase (p-AMPK) and Sirtuin 1 (SIRT1) protein expressions. The effect of genistein on reducing lipid droplets accumulation and upregulating p-AMPK protein level was blocked entirely when pretreated with SIRT1 inhibitor. These results implied that SIRT1 is required to activate AMPK. Furthermore, genistein treatment significantly upregulated the SIRT1 protein level when pretreated with AMPK inhibitor. We demonstrated that the activation of estrogen receptor beta-Forkhead box O1-Nicotinamide phosphoribosyl transferase (ER beta-FOXO1-Nampt) signaling pathway upregulated the NAD(+) concentration in hepatocytes, and activated SIRT1 ultimately. In summary, we demonstrated that genistein suppressed lipid droplets accumulation in chicken hepatocytes by activating SIRT1-AMPK. The SIRT1-AMPK signaling pathway was mediated by ER beta-FOXO1-Nampt. These findings increase our understanding of the mechanisms of genistein on fat reduction, and provide compelling evidence for it as a nutritional supplement to prevent excessive fat deposition and lipid metabolism-related diseases in animals and even humans.