Coffee consumption has been shown to reduce the risk of developing type 2 diabetes mellitus (T2DM) in humans; however, the exact mechanism is not completely understood. Here, we demonstrate that N-caffeoyltryptophan (CTP), an ingredient of coffee, enhances adipogenic differentiation and promotes glucose uptake into adipocytes. CTP increased lipid accumulation and adipogenic markers (PPARγ, C/EBPα, and FABP4) expression in mouse 3T3-L1 preadipocyte cell lines and primary preadipocytes. In addition, CTP promoted glucose uptake in 3T3-L1 cells. In the oral glucose tolerance test, daily administration of CTP (30 mg/kg/day, i.p.) for a week reduced blood glucose levels in mice. In 3T3-L1 cells, adipogenic differentiation and increased adipogenic markers expression induced by CTP were inhibited by U0126, a selective MEK1/2 inhibitor. Furthermore, mRNA induction of Pparg by CTP was abrogated in SIRT1 siRNA-transfected 3T3-L1 cells. These results suggest the involvement of the MEK/ERK signaling and SIRT1 in the mechanism of adipogenic function of CTP. Taken together, CTP might contribute to the reduction in postprandial glycemia and a subsequent reduction in onset risk for T2DM.

咖啡消费已被证明可以降低人类患 2 型糖尿病 (T2DM) 的风险；然而，确切的机制尚不完全清楚。在这里，我们证明N-咖啡酰色氨酸 (CTP) 是咖啡的一种成分，可增强脂肪形成分化并促进脂肪细胞摄取葡萄糖。CTP 增加了小鼠 3T3-L1 前脂肪细胞系和原代前脂肪细胞中的脂质积累和脂肪生成标志物（PPARγ、C/EBPα 和 FABP4）的表达。此外，CTP 促进 3T3-L1 细胞的葡萄糖摄取。在口服葡萄糖耐量试验中，连续一周每天给予 CTP（30 mg/kg/天，腹腔注射）可降低小鼠的血糖水平。在 3T3-L1 细胞中，CTP 诱导的脂肪形成分化和脂肪形成标志物表达增加被选择性 MEK1/2 抑制剂 U0126 抑制。此外， Pparg的 mRNA 诱导CTP 的作用在 SIRT1 siRNA 转染的 3T3-L1 细胞中被消除。这些结果表明 MEK/ERK 信号和 SIRT1 参与了 CTP 的脂肪形成功能机制。总之，CTP 可能有助于降低餐后血糖和随后降低 T2DM 的发病风险。