Armstrong M B, Towle H C
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1197-204. doi: 10.1152/ajpendo.2001.281.6.E1197.
The discovery of homologs of the brown fat uncoupling protein(s) (UCP) UCP-2 and UCP-3 revived the hypothesis of uncoupling protein involvement in the regulation of energy metabolism. Thus we hypothesized that UCP-2 would be regulated in the hepatocyte by fatty acids, which are known to control other energy-related metabolic processes. Treatment with 250 microM palmitic acid was without effect on UCP-2 expression, whereas 250 microM oleic acid exhibited a modest eightfold increase. Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, exerted a 50-fold upregulation of UCP-2 that was concentration dependent. This effect was seen within 12 h and was maximal by 36 h. Aspirin blocked the induction of UCP-2 by EPA, indicating involvement of the prostaglandin pathway. Hepatocytes treated with arachidonic acid, the immediate precursor to the prostaglandins, also exhibited an aspirin-inhibitable increase in UCP-2 levels, further supporting the involvement of prostaglandins in regulating hepatic UCP-2. The peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist Wy-14643 stimulated UCP-2 mRNA levels as effectively as EPA. These data indicate that UCP-2 is upregulated by polyunsaturated fatty acids, potentially through a prostaglandin/PPARalpha-mediated pathway.
棕色脂肪解偶联蛋白（UCP）UCP - 2和UCP - 3同源物的发现，使解偶联蛋白参与能量代谢调节的假说再度兴起。因此，我们推测UCP - 2在肝细胞中会受到脂肪酸的调节，而脂肪酸已知可控制其他与能量相关的代谢过程。用250微摩尔棕榈酸处理对UCP - 2表达没有影响，而250微摩尔油酸使UCP - 2表达适度增加了8倍。二十碳五烯酸（EPA），一种多不饱和脂肪酸，使UCP - 2上调了50倍，且呈浓度依赖性。这种效应在12小时内即可观察到，36小时时达到最大。阿司匹林阻断了EPA对UCP - 2的诱导作用，表明前列腺素途径参与其中。用花生四烯酸（前列腺素的直接前体）处理的肝细胞，UCP - 2水平也出现了阿司匹林可抑制的升高，进一步支持了前列腺素参与调节肝脏UCP - 2的观点。过氧化物酶体增殖物激活受体α（PPARα）激动剂Wy - 14643刺激UCP - 2 mRNA水平的效果与EPA一样有效。这些数据表明，UCP - 2可能通过前列腺素/PPARα介导的途径被多不饱和脂肪酸上调。
