Shabalina Irina G, Backlund Emma C, Bar-Tana Jacob, Cannon Barbara, Nedergaard Jan
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):642-50. doi: 10.1016/j.bbabio.2008.04.038. Epub 2008 May 1.
In the present investigation, we have utilized the availability of UCP1(-/-) mice to examine a wide range of previously proposed lipid activators of Uncoupling Protein 1 (UCP1) in its native environment, i.e. in the brown-fat cells. A non-metabolizable fatty acid analogue, beta,beta cent-methyl-substituted hexadecane alpha,omega-dicarboxylic acid (Medica-16) is a potent UCP1 (re)activator in brown-fat cells, despite its bipolar structure. All-trans-retinoic acid activates UCP1 within cells, whereas beta-carotene only does so after metabolism. The UCP1-dependent effects of fatty acids are positively correlated with their chain length. Medium-chain fatty acids are potent UCP1 activators in cells, despite their lack of protonophoric properties in mitochondrial membranes. Thus, neither the ability to be metabolized nor an innate uncoupling/protonophoric ability is a necessary property of UCP1 activators within brown-fat cells.
在本研究中，我们利用UCP1基因敲除小鼠来检测一系列先前提出的解偶联蛋白1（UCP1）的脂质激活剂，这些激活剂是在其天然环境中，即在棕色脂肪细胞中发挥作用。一种不可代谢的脂肪酸类似物，β,β-二甲基取代的十六烷α,ω-二羧酸（Medica-16），尽管其具有双极结构，但却是棕色脂肪细胞中一种有效的UCP1（再）激活剂。全反式维甲酸在细胞内激活UCP1，而β-胡萝卜素仅在代谢后才激活UCP1。脂肪酸对UCP1的依赖性作用与其链长呈正相关。中链脂肪酸是细胞中有效的UCP1激活剂，尽管它们在线粒体内膜中缺乏质子载体特性。因此，可代谢能力和固有的解偶联/质子载体能力都不是棕色脂肪细胞中UCP1激活剂的必要特性。
