Brown J M, Halvorsen Y D, Lea-Currie Y R, Geigerman C, McIntosh M
Graduate Program in Nutrition, University of North Carolina at Greensboro, 27402, USA.
J Nutr. 2001 Sep;131(9):2316-21. doi: 10.1093/jn/131.9.2316.
We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs. trans-10, cis-12 CLA on TG content; 3) whether chronic linoleic acid supplementation could rescue the TG content of CLA-treated cultures; and 4) whether trans-10, cis-12-mediated reduction in cellular TG was due to decreased lipogenesis and/or increased lipolysis. In expt. 1, the TG content [micromol/(L x 10(6) cells)] increased as both seeding density and TZD concentration increased. For example, cultures seeded at 4 x 10(4) cells/cm(2) and supplemented with 10 micromol/L BRL 49653 had 10-fold more TG than similarly seeded cultures without BRL 49653. In expt. 2, TG content decreased as the level of trans-10, cis-12 CLA increased from 1 to 10 micromol/L, whereas the TG content increased with increasing concentrations of either linoleic acid or cis-9, trans-11 CLA. In expt. 3, linoleic acid supplementation restored the TG content of cultures treated with trans-10, cis-12 CLA compared with cultures treated with CLA alone, suggesting that attenuation of TG content by CLA is reversible. In expt. 4, glucose incorporation into total lipid decreased with increasing levels of trans-10, cis-12 CLA, whereas neither CLA isomer acutely affected lipolysis. These data suggest that the reported antiobesity actions of a supplement containing a crude mixture of CLA isomers given to humans may be due to inhibition of lipogenesis by the trans-10, cis-12 isomer.
我们之前已经表明,市售的共轭亚油酸(CLA)异构体混合物以及CLA的反式-10,顺式-12异构体均可降低甘油三酯(TG)含量,并在小鼠3T3-L1前脂肪细胞的分化培养中诱导细胞凋亡。然而,CLA异构体对人(前)脂肪细胞分化的影响尚不清楚。因此,我们使用从人脂肪组织分离的基质血管细胞原代培养物进行了一系列研究,以确定:1)接种密度和噻唑烷二酮(TZD)浓度对TG含量的影响;2)顺式-9,反式-11 CLA与反式-10,顺式-12 CLA对TG含量的慢性剂量反应;3)长期补充亚油酸是否可以挽救CLA处理的培养物中的TG含量;以及4)反式-10,顺式-12介导的细胞TG减少是否归因于脂肪生成减少和/或脂肪分解增加。在实验1中,TG含量[微摩尔/(升×10^6个细胞)]随着接种密度和TZD浓度的增加而增加。例如,以4×10^4个细胞/平方厘米接种并补充10微摩尔/升BRL 49653的培养物中的TG含量比未添加BRL 49653的类似接种培养物高10倍。在实验2中,随着反式-10,顺式-12 CLA水平从1微摩尔/升增加到10微摩尔/升,TG含量降低,而随着亚油酸或顺式-9,反式-11 CLA浓度的增加,TG含量增加。在实验3中,与单独用CLA处理的培养物相比,补充亚油酸可恢复用反式-10,顺式-12 CLA处理的培养物中的TG含量,这表明CLA对TG含量的降低是可逆的。在实验4中,随着反式-10,顺式-12 CLA水平的增加,葡萄糖掺入总脂质的量减少,而两种CLA异构体均未急性影响脂肪分解。这些数据表明,报道的给予人类的含有CLA异构体粗混合物的补充剂的抗肥胖作用可能是由于反式-10,顺式-12异构体抑制脂肪生成所致。