Division of Food Science and Biotechnology, Department of Agriculture, Graduated School of Science and Technology, Shinshu University, Kamiina, Nagano, Japan.
Division of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Kamiina, Nagano, Japan.
Biosci Biotechnol Biochem. 2022 Jan 24;86(2):260-272. doi: 10.1093/bbb/zbab203.
Genistein exerts antiadipogenic effects, but its target molecules remain unclear. Here, we delineated the molecular mechanism underlying the antiadipogenic effect of genistein. A pulldown assay using genistein-immobilized beads identified adenine nucleotide translocase-2 as a genistein-binding protein in adipocytes. Adenine nucleotide translocase-2 exchanges ADP/ATP through the mitochondrial inner membrane. Similar to the knockdown of adenine nucleotide translocase-2, genistein treatment decreased ADP uptake into the mitochondria and ATP synthesis. Genistein treatment and adenine nucleotide translocase-2 knockdown suppressed adipogenesis and increased phosphorylation of AMP-activated protein kinase. Adenine nucleotide translocase-2 knockdown reduced the transcriptional activity of CCAAT/enhancer-binding protein β, whereas AMP-activated protein kinase inhibition restored the suppression of adipogenesis by adenine nucleotide translocase-2 knockdown. These results indicate that genistein interacts directly with adenine nucleotide translocase-2 to suppress its function. The downregulation of adenine nucleotide translocase-2 reduces the transcriptional activity of CCAAT/enhancer-binding protein β via activation of AMP-activated protein kinase, which consequently represses adipogenesis.
染料木黄酮具有抗脂肪生成作用，但其靶分子仍不清楚。在这里，我们阐述了染料木黄酮抗脂肪生成作用的分子机制。用染料木黄酮固定珠进行的下拉实验鉴定出腺嘌呤核苷酸转位酶-2 是脂肪细胞中与染料木黄酮结合的蛋白质。腺嘌呤核苷酸转位酶-2 通过线粒体内膜交换 ADP/ATP。类似于腺嘌呤核苷酸转位酶-2 的敲低，染料木黄酮处理会减少 ADP 进入线粒体和 ATP 合成。染料木黄酮处理和腺嘌呤核苷酸转位酶-2 敲低抑制脂肪生成并增加 AMP 激活的蛋白激酶磷酸化。腺嘌呤核苷酸转位酶-2 敲低会降低 CCAAT/增强子结合蛋白β的转录活性，而 AMP 激活的蛋白激酶抑制会恢复腺嘌呤核苷酸转位酶-2 敲低对脂肪生成的抑制作用。这些结果表明，染料木黄酮与腺嘌呤核苷酸转位酶-2 直接相互作用以抑制其功能。腺嘌呤核苷酸转位酶-2 的下调通过激活 AMP 激活的蛋白激酶降低 CCAAT/增强子结合蛋白β 的转录活性，从而抑制脂肪生成。
