Tsai Yung-Chieh, Yang Bo-Cheng, Peng Wen-Huang, Lee Yen-Mei, Yen Mao-Hsiung, Cheng Pao-Yun
Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan; Department of Medicine, Taipei Medical University, Taipei; Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
Phytomedicine. 2017 Jul 15;31:11-17. doi: 10.1016/j.phymed.2017.05.005. Epub 2017 May 22.
Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Raspberry ketone (RK), a major aromatic compound in red raspberry, was recently reported to possess anti-obesity effects. However, its mechanisms are unclear.
Adipogenesis plays a critical role in obesity and, therefore, this study aimed to investigate the effect and mechanisms of action of RK on adipogenesis in 3T3-L1 preadipocytes.
3T3-L1 preadipocytes were differentiated in medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Adipocyte lipid contents were determined using oil-red O staining while adipogenic transcription factor and lipogenic protein expressions were determined using western blotting.
RK (300-400µM) strongly inhibited lipid accumulation during 3T3-L1 preadipocyte differentiation into adipocytes. RK reduced the CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferation-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4) expressions and increased heme oxygenase-1 (HO-1), Wnt10b, and β-catenin expressions in 3T3-L1 adipocytes. Additionally, RK inhibited lipid accumulation, and adipogenic transcription factor and lipogenic protein expressions were all decreased by inhibiting HO-1 or β-catenin using tin protoporphyrin (SnPP) or β-catenin short-interfering RNA (siRNA), respectively. Furthermore, Wnt10b and β-catenin expressions were negatively regulation by SnPP.
RK may exert anti-adipogenic effects through modulation of the HO-1/Wnt/beta-catenin signaling pathway.
肥胖是由体内脂肪过度堆积引起的，与复杂的代谢性疾病密切相关。树莓酮（RK）是红树莓中的一种主要芳香化合物，最近有报道称其具有抗肥胖作用。然而，其作用机制尚不清楚。
脂肪生成在肥胖中起关键作用，因此，本研究旨在探讨RK对3T3-L1前脂肪细胞脂肪生成的影响及其作用机制。
3T3-L1前脂肪细胞在含有胰岛素、地塞米松和1-甲基-3-异丁基黄嘌呤的培养基中分化。用油红O染色法测定脂肪细胞脂质含量，用蛋白质免疫印迹法测定脂肪生成转录因子和脂肪生成蛋白表达。
RK（300-400μM）强烈抑制3T3-L1前脂肪细胞分化为脂肪细胞过程中的脂质积累。RK降低了3T3-L1脂肪细胞中CCAAT/增强子结合蛋白-α（C/EBP-α）、过氧化物酶体增殖物激活受体-γ（PPAR-γ）、脂肪酸合酶（FAS）和脂肪酸结合蛋白4（FABP4）的表达，并增加了血红素加氧酶-1（HO-1）、Wnt10b和β-连环蛋白的表达。此外，分别使用锡原卟啉（SnPP）抑制HO-1或使用β-连环蛋白小干扰RNA（siRNA）抑制β-连环蛋白后，RK抑制脂质积累以及脂肪生成转录因子和脂肪生成蛋白表达均降低。此外，SnPP对Wnt10b和β-连环蛋白表达呈负调控。
RK可能通过调节HO-1/Wnt/β-连环蛋白信号通路发挥抗脂肪生成作用。
