Peng Li, Lu Yanting, Xu Yuhui, Hu Jing, Wang Fang, Zhang Yumei, Xiong Wenyong
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
University of the Chinese Academy of Sciences, Beijing, 100049, China.
Nat Prod Bioprospect. 2017 Jun;7(3):225-234. doi: 10.1007/s13659-017-0127-9. Epub 2017 May 19.
Obesity is crucially involved in many metabolic diseases, such as type 2 diabetes, cardiovascular disease and cancer. Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity. In this study, we investigated the effect of pyrocincholic acid 3β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (PAQG), a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma, on adipogenesis and lipid metabolism in 3T3-L1 adipocytes. The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process. PAQG significantly reduced the adipogenesis, adiponectin secretion and the expression level of key transcription factors related to adipogenesis, such as PPARγ, C/EBPβ, C/EBPα, and FABP4. Moreover, PAQG increased the levels of FFA and glycerol in medium and reduced TG level in mature adipocytes. Interestingly, PAQG not only promoted the activation of AMPK and genes involved in fatty oxidation including PDK4 and CPT1a, but also inhibited those genes involved in fatty acid biosynthesis, such as SREBP1c, FAS, ACCα and SCD1. In conclusion, PAQG inhibits the differentiation and regulates lipid metabolism of 3T3-L1 cells via AMPK pathway, suggesting that PAQG may be a novel and promising natural product for the treatment of obesity and hyperlipidemia.
肥胖与许多代谢性疾病密切相关，如2型糖尿病、心血管疾病和癌症。调节脂肪细胞的数量或大小被认为是治疗肥胖的一种潜在方法。在本研究中，我们研究了从毛钩藤中提取的27-去甲齐墩果酸皂苷焦袂康酸3β-O-β-D-奎诺吡喃糖基-28-O-β-D-吡喃葡萄糖苷（PAQG）对3T3-L1脂肪细胞脂肪生成和脂质代谢的影响。在分化过程中，将3T3-L1前脂肪细胞与载体或PAQG孵育6天。PAQG显著降低了脂肪生成、脂联素分泌以及与脂肪生成相关的关键转录因子如PPARγ、C/EBPβ、C/EBPα和FABP4的表达水平。此外，PAQG增加了培养基中游离脂肪酸（FFA）和甘油的水平，并降低了成熟脂肪细胞中的甘油三酯（TG）水平。有趣的是，PAQG不仅促进了AMPK的激活以及参与脂肪酸氧化的基因如PDK4和CPT1a的表达，还抑制了参与脂肪酸生物合成的基因如SREBP1c、FAS、ACCα和SCD1的表达。总之，PAQG通过AMPK途径抑制3T3-L1细胞的分化并调节脂质代谢，表明PAQG可能是一种用于治疗肥胖和高脂血症的新型且有前景的天然产物。
