Kim Nami, Kim Hong Min, Lee Eun Soo, Lee Jung Ok, Lee Hye Jeong, Lee Soo Kyung, Moon Ji Wook, Kim Ji Hae, Kim Joong Kwan, Kim Su Jin, Park Sun Hwa, Chung Choon Hee, Kim Hyeon Soo
Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, South Korea.
PLoS One. 2015 Mar 10;10(3):e0120104. doi: 10.1371/journal.pone.0120104. eCollection 2015.
Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.
二苯甲酰甲烷（DBM）已被证明对人体健康具有多种有益作用。然而，其作用机制尚不清楚。在本研究中，DBM增加了AMP激活的蛋白激酶（AMPK）的磷酸化，并刺激了骨骼肌细胞系中的葡萄糖摄取。用小干扰RNA（siRNA）敲低AMPK以及用AMPK抑制剂抑制均阻断了DBM诱导的葡萄糖摄取。DBM增加了细胞内钙的浓度，而STO-609（一种钙/钙调蛋白依赖性蛋白激酶抑制剂）消除了因DBM导致的葡萄糖摄取增加。DBM刺激了p38丝裂原活化蛋白激酶（p38 MAPK）的磷酸化，这被AMPK抑制剂化合物C预处理所阻断。DBM增加了4型葡萄糖转运蛋白（GLUT4）的表达。DBM还以AMPK依赖性方式增加了GLUT4向质膜的转位。此外，DBM抑制了高脂饮食喂养小鼠的体重增加，并防止了肝脏和腹部的脂肪堆积。在脂肪前体细胞中，DBM降低了脂肪酸合成的限速酶乙酰辅酶A羧化酶（ACC）的活性。DBM以AMPK依赖性方式抑制了脂肪生成基因脂肪酸合酶（FAS）的表达。这些结果表明，DBM有益的代谢作用可能归因于通过AMPK调节骨骼肌中的葡萄糖摄取以及抑制脂肪前体细胞中的脂肪生成。
