Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Life Sci. 2022 Aug 15;303:120676. doi: 10.1016/j.lfs.2022.120676. Epub 2022 May 28.
Genistein, the most abundance of phytoestrogens in soybeans, has beneficial effects in regulating metabolism-related disease; however, there is few available literatures about whether genistein regulates glucose metabolism that in turn affects the lipid accumulation in animals or humans. The current study showed that genistein promoted glucose uptake by enhancing glucose transporter-2 (GLUT2) protein level; and it also increased the activity of phosphofructokinase-1 (PFK) and pyruvate dehydrogenase (PDH), and the mRNA level of succinate dehydrogenase (SDH) both in broiler chickens or hepatocytes. Moreover, genistein obviously increased the p-LKB1 and p-AMPKα protein levels both in vivo and in vitro. Furthermore, the enhancement of genistein on glucose uptake and catabolism were reversed in hepatocytes pre-treated with AMPK inhibitor Compound C, and the increasing of genistein on the p-LKB1 and p-AMPKα protein levels were also reversed in hepatocytes pre-treated with PKA inhibitor H89. Importantly, the results showed that genistein simultaneously increased the estrogen receptor β (ERβ) and G protein-coupled estrogen receptor (GPER) protein levels, but the elevation effect of genistein on cAMP content was completely reversed in hepatocytes pre-treated with GPER antagonist G15, rather than ERβ inhibitor PHTPP. Meanwhile, the increasing of p-LKB1 and p-AMPKα protein levels induced by genistein were also reversed in hepatocytes pre-treated with G15. Collectively, our data demonstrated that genistein improves glucose metabolism via activating the GPER-mediated cAMP/PKA-AMPK signaling pathway. These findings provide theoretical basis for genistein as a promising nutritional supplemental to alleviate metabolism disorders and related diseases in animals or even humans.
染料木黄酮是大豆中最丰富的植物雌激素，对调节代谢相关疾病有有益作用；然而，关于染料木黄酮是否通过调节葡萄糖代谢进而影响动物或人类的脂质积累，相关文献较少。本研究表明，染料木黄酮通过增强葡萄糖转运蛋白-2（GLUT2）蛋白水平促进葡萄糖摄取；还增加了磷酸果糖激酶-1（PFK）和丙酮酸脱氢酶（PDH）的活性，以及琥珀酸脱氢酶（SDH）的 mRNA 水平，无论是在肉鸡还是肝细胞中。此外，染料木黄酮明显增加了体内和体外 LKB1 和 AMPKα 的磷酸化水平。此外，在 AMPK 抑制剂 Compound C 预处理的肝细胞中，染料木黄酮对葡萄糖摄取和分解代谢的增强作用被逆转，而在 PKA 抑制剂 H89 预处理的肝细胞中，染料木黄酮对 LKB1 和 AMPKα 蛋白水平的增加作用也被逆转。重要的是，结果表明，染料木黄酮同时增加了雌激素受体β（ERβ）和 G 蛋白偶联雌激素受体（GPER）的蛋白水平，但在 GPER 拮抗剂 G15 预处理的肝细胞中，染料木黄酮对 cAMP 含量的升高作用完全被逆转，而不是 ERβ 抑制剂 PHTPP。同时，G15 预处理的肝细胞中，染料木黄酮诱导的 p-LKB1 和 p-AMPKα 蛋白水平的增加也被逆转。综上所述，我们的数据表明，染料木黄酮通过激活 GPER 介导的 cAMP/PKA-AMPK 信号通路改善葡萄糖代谢。这些发现为染料木黄酮作为一种有前途的营养补充剂，以减轻动物甚至人类的代谢紊乱和相关疾病提供了理论依据。
