Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes
Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes
复制标题
DOI：
10.1007/s11745-000-0599-6
复制
发表时间：
2000-08-01
期刊：
影响因子：
1.9
通讯作者：
McIntosh, M
中科院分区：
文献类型：
--
作者：
Evans, M;Geigerman, C;McIntosh, M
在生理培养条件下，研究共轭亚油酸(CLA)异构体对3T3-L1前脂肪细胞增殖和分化的影响。用白蛋白[牛血清白蛋白(BSA)载体]或亚油酸(LA)处理的培养物作为对照。在增殖研究(Exyt.1)中，细胞在含有CLA异构体或纯LA的粗混合物的培养液中培养4d，前脂肪细胞的增殖(细胞数量，H-3-胸腺嘧啶核苷掺入DNA)随着CLA水平的增加而下降。相比之下，LA对DNA合成没有影响。在实验2a中，在接下来的6d中，融合后的培养物在含有0、10、50或200亩M的CLA或LA的粗混合物中生长。融合后的培养物添加50-200亩M的CLA含有较少的甘油三酯(TG)，且体积比添加类似量LA的培养物小。在实验2b中，在培养的第1、3、6或9天，在融合后添加200 CIM的CLA异构体或LA粗混合物。在培养3天后，添加200 mU M CFA的培养物的TG含量与对照组和添加LA的培养物相比有明显的差异。实验3a和3b检验了脂肪酸载体(牛血清白蛋白与乙醇)或培养物的维生素E状态(+/-0.2 mMα-生育酚)是否改变了共轭亚油酸对前脂肪细胞TG含量的影响。在实验3a中，无论脂肪酸处理如何，乙醇处理的培养物都比非乙醇处理的培养物有更多的甘油三酯。在实验3b中，在没有补充维生素E的情况下，用100mM的CLA或反式-10，顺-12型CLA异构体处理6d，培养6d的细胞的甘油三酯低于含维生素E的CLA处理的细胞。在实验4中，将融合后的培养物在含有100mU的CLA或CLA异构体或反式-10，顺-12型CLA的粗混合物中培养24-96h，以评价CLA对细胞周期和细胞凋亡指数的影响。100mM共轭亚油酸处理24-90h的细胞凋亡率高于牛血清白蛋白或乳酸处理的细胞。此外，共轭亚油酸处理48h后，S期细胞数较对照少。反式-10，顺-12共轭亚油酸异构体的影响比粗品共轭亚油酸异构体的影响更明显。这些数据表明，CLA可能通过抑制(前)脂肪细胞的增殖、降低TG含量和/或诱导其凋亡来发挥其抗肥胖作用。
Tour sets of experiments were conducted to Examine the influence of conjugated linoleic acid (CLA) isomers during proliferation and differentiation of cultures of 3T3-L1 preadipocytes using physiological culturing conditions. Cultures treated with either albumin [bovine serum albumin (BSA) vehicle] or linoleic acid (LA) served as controls. For the proliferation study (Exyt.1), cells were cultured in media containing a crude mixture of CLA isomers or pure LA at 0, 10, 50, or 200 mu M for 4 d. Preadipocyte proliferation (cell number, H-3-thymidine incorporation into DNA) decreased as the level of CLA increased in the cultures. In contrast, LA had no impact on DNA synthesis. In Experiment 2a, postconfluent cultures were grown in media containing a crude mixture of CLA isomers or LA at 0, 10, 50, or 200 mu M for the next 6 d. Postconfluent cultures supplemented with 50-200 mu M CLA had less triglyceride (TG) and were smaller in size than cultures supplemented with similar amounts of LA. In Experiment 2b, postconfluent cultures supplemented with 200 CIM of a crude mixture of CLA isomers or LA were harvested on days 1, 3, 6, or 9. Differences in TG content of cultures supplemented with 200 mu M CFA compared to control and LA-supplemented cultures became apparent after 3 d of culture. Experiments 3a and 3b examined whether the fatty acid vehicle (BSA vs. ethanol) or the vitamin E status (+/-0.2 mM alpha-tocopherol) of the cultures altered CLA's impact on preadipocyte TG content. In Experiment 3a, ethanol-treated cultures had more TG than non-ethanol-treated cultures regardless of the fatty acid treatment. In Experiment 3b, cultures treated with 100 mu M of either a crude mixture of CLA or the trans-10, cis-12 CLA isomer without supplemental vitamin E For 6 d had less TG than CLA-treated cultures containing vitamin E. In Experiment 4, postconfluent cultures were grown in media containing 100 mu M LA or either a crude mixture of CLA isomers or the trans-10,cis-12 CLA isomer for 24-96 h to assess CLA's influence on the cell cycle and indices of apoptosis. Cultures treated with 100 mu M CLA for 24-90 h had more apoptotic cells than BSA- or LA-treated cultures. Furthermore, cultures treated for 48 h with CLA had fewer cells in the S-phase than control cultures. The effects of the trans-10,cis-12 CLA isomer were more pronounced than those of the crude mixture of CLA isomers. These data suggest that CLA may exert its antiobesity effects by inhibiting proliferation, attenuating TG content, and/or inducing apoptosis in (pre)adipocytes.