Department of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Nutrients. 2022 Apr 8;14(8):1551. doi: 10.3390/nu14081551.
Genistein is an isoflavone phytoestrogen that has been shown to improve obesity; however, the underlying molecular mechanisms involved therein have not been clearly elucidated. In this study, we administered genistein to high-fat diet-induced obese mice to investigate its effect on hepatic gluconeogenesis. The results showed that genistein treatment significantly inhibited body weight gain, hyperglycemia, and adipose and hepatic lipid deposition in high-fat diet-induced obese mice. Glucose tolerance test (GTT), insulin tolerance test (ITT) and pyruvate tolerance test (PTT) showed that genistein treatment significantly inhibited gluconeogenesis and improved insulin resistance in obese mice. In addition, this study also found that genistein could promote the expression of miR-451 in vitro and in vivo, and the dual-luciferase reporter system showed that (glucose-6-phosphatase) may be a target gene of miR-451. Both genistein treatment and in vivo injection of miR-451 agomir significantly inhibited gluconeogenesis and inhibited the expression of and (glycerol kinase, a known target gene of miR-451). In conclusion, genistein may inhibit gluconeogenesis in obese mice by regulating the expression of and through miR-451. These results may provide insights into the functions of miR-451 and food-derived phytoestrogens in ameliorating and preventing gluconeogenesis-related diseases.
染料木黄酮是一种异黄酮植物雌激素，已被证明可以改善肥胖；然而，其涉及的潜在分子机制尚未得到明确阐明。在这项研究中，我们给高脂肪饮食诱导肥胖的小鼠施用染料木黄酮，以研究其对肝糖异生的影响。结果表明，染料木黄酮处理显著抑制了高脂肪饮食诱导肥胖小鼠的体重增加、高血糖以及脂肪和肝脏脂质沉积。葡萄糖耐量试验（GTT）、胰岛素耐量试验（ITT）和丙酮酸耐量试验（PTT）表明，染料木黄酮处理显著抑制了肥胖小鼠的糖异生并改善了胰岛素抵抗。此外，本研究还发现，染料木黄酮可以在体外和体内促进 miR-451 的表达，双荧光素酶报告系统表明（葡萄糖-6-磷酸酶）可能是 miR-451 的一个靶基因。染料木黄酮处理和体内注射 miR-451 agomir 均显著抑制了糖异生，并抑制了和（甘油激酶，miR-451 的已知靶基因）的表达。综上所述，染料木黄酮可能通过调节 miR-451 的表达来抑制肥胖小鼠的糖异生。这些结果可能为 miR-451 和食物来源的植物雌激素在改善和预防与糖异生相关的疾病方面的功能提供新的见解。
