Hwang Jin-Taek, Park In-Ja, Shin Jang-In, Lee Yun Kyoung, Lee Seong Kyu, Baik Haing Woon, Ha Joohun, Park Ock Jin
Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea.
Biochem Biophys Res Commun. 2005 Dec 16;338(2):694-9. doi: 10.1016/j.bbrc.2005.09.195. Epub 2005 Oct 11.
Phytochemicals such as soy isoflavone genistein have been reported to possess therapeutic effects for obesity, diabetes, and cardiovascular diseases. In the present study, the molecular basis of selective phytochemicals with emphasis on their ability to control intracellular signaling cascades of AMP-activated kinase (AMPK) responsible for the inhibition of adipogenesis was investigated. Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of anti-obesity. Hypothalamic AMPK was found to integrate nutritional and hormonal signals modulating feeding behavior and energy expenditure. We have investigated the effects of genistein, EGCG, and capsaicin on adipocyte differentiation in relation to AMPK activation in 3T3-L1 cells. Genistein (20-200muM) significantly inhibited the process of adipocyte differentiation and led to apoptosis of mature adipocytes. Genistein, EGCG, and capsaicin stimulated the intracellular ROS release, which activated AMPK rapidly. We suggest that AMPK is a novel and critical component of both inhibition of adipocyte differentiation and apoptosis of mature adipocytes by genistein or EGCG or capsaicin further implying AMPK as a prime target of obesity control.
据报道，大豆异黄酮染料木黄酮等植物化学物质对肥胖、糖尿病和心血管疾病具有治疗作用。在本研究中，研究了选择性植物化学物质的分子基础，重点是它们控制负责抑制脂肪生成的AMP激活蛋白激酶（AMPK）细胞内信号级联反应的能力。最近，进化上保守的丝氨酸/苏氨酸激酶AMPK成为抗肥胖的一个可能靶点分子。发现下丘脑AMPK整合调节进食行为和能量消耗的营养和激素信号。我们研究了染料木黄酮、表没食子儿茶素没食子酸酯（EGCG）和辣椒素对3T3-L1细胞中与AMPK激活相关的脂肪细胞分化的影响。染料木黄酮（20-200μM）显著抑制脂肪细胞分化过程，并导致成熟脂肪细胞凋亡。染料木黄酮、EGCG和辣椒素刺激细胞内活性氧释放，从而迅速激活AMPK。我们认为，AMPK是染料木黄酮或EGCG或辣椒素抑制脂肪细胞分化和成熟脂肪细胞凋亡的一个新的关键组成部分，这进一步表明AMPK是控制肥胖的主要靶点。
