College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
Food Funct. 2020 Mar 1;11(3):2418-2426. doi: 10.1039/c9fo00861f. Epub 2020 Mar 4.
Obesity and diabetes mellitus have become major health problems worldwide. In recent years, genistein has been found to be capable of inhibiting obesity and alleviating insulin resistance. However, the molecular mechanism of genistein against obesity is still not fully understood. In this study, we used 3T3-L1 preadipocytes and obese mice as models to explore the molecular mechanism of genistein against obesity. We found that genistein can inhibit obesity and downregulate the expression of miR-222 in mouse adipose tissue. In 3T3-L1 preadipocytes, treatment with miR-222 inhibitor or genistein reduced the expression of miR-222 and promoted lipid decomposition, while miR-222 treatment increased the expression of miR-222 and inhibited lipolysis. Moreover, the dual-luciferase reporter assay system confirmed that BTG2 and adipor1 are the target genes of miR-222. Experiments conducted in vitro and in vivo suggest that genistein may regulate lipid metabolism in the adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1. Our findings provide a new epigenetic mechanism underpinning the ability of genistein to resist obesity. These results may provide a reference point for the dietary treatment of obesity and type 2 diabetes mellitus.
肥胖和糖尿病已成为全球主要的健康问题。近年来，研究发现染料木黄酮能够抑制肥胖并缓解胰岛素抵抗。然而，染料木黄酮防治肥胖的分子机制尚不完全清楚。本研究以 3T3-L1 前脂肪细胞和肥胖小鼠为模型，探讨了染料木黄酮防治肥胖的分子机制。结果发现，染料木黄酮能够抑制肥胖，并下调肥胖小鼠脂肪组织中 miR-222 的表达。在 3T3-L1 前脂肪细胞中，用 miR-222 抑制剂或染料木黄酮处理能够降低 miR-222 的表达并促进脂肪分解，而 miR-222 处理则增加 miR-222 的表达并抑制脂肪分解。此外，双荧光素酶报告基因检测系统证实，BTG2 和 adipor1 是 miR-222 的靶基因。体外和体内实验表明，染料木黄酮可能通过调节 miR-222 及其靶基因 BTG2 和 adipor1 的表达来调节肥胖小鼠脂肪组织中的脂质代谢。本研究为染料木黄酮抵抗肥胖的表观遗传机制提供了新的证据，可能为肥胖和 2 型糖尿病的饮食治疗提供参考。
