König Bettina, Koch Alexander, Giggel Karen, Dordschbal Batsuch, Eder Klaus, Stangl Gabriele I
Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Biochim Biophys Acta. 2008 Jun;1780(6):899-904. doi: 10.1016/j.bbagen.2008.03.002. Epub 2008 Mar 18.
Peroxisome proliferator-activated receptor (PPAR)-alpha mediates an adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketone body synthesis. Ketone bodies are transferred in and out of cells by monocarboxylate transporter (MCT)-1. In this study we observed for the first time that activation of PPARalpha in rats by clofibrate treatment or fasting increased hepatic mRNA concentration of MCT1. In Fao rat hepatoma cells, incubation with the PPARalpha agonist WY 14,643 increased mRNA concentration of MCT1 whereas the PPARgamma agonist troglitazone did not. To elucidate whether up-regulation of MCT1 is indeed mediated by PPARalpha we treated wild-type and PPARalpha-null mice with WY 14,643. In wild-type mice, treatment with WY 14,643 increased mRNA concentrations of MCT1 in liver, kidney and small intestine whereas no up-regulation was observed in PPARalpha-null mice.
过氧化物酶体增殖物激活受体（PPAR）-α 通过上调参与脂肪酸氧化和酮体合成的基因来介导对禁食的适应性反应。酮体通过单羧酸转运体（MCT）-1 进出细胞。在本研究中，我们首次观察到，用氯贝丁酯治疗或禁食激活大鼠体内的 PPARα 会增加肝脏中 MCT1 的 mRNA 浓度。在 Fao 大鼠肝癌细胞中，用 PPARα 激动剂 WY 14,643 孵育会增加 MCT1 的 mRNA 浓度，而 PPARγ 激动剂曲格列酮则不会。为了阐明 MCT1 的上调是否确实由 PPARα 介导，我们用 WY 14,643 处理野生型和 PPARα 基因敲除小鼠。在野生型小鼠中，用 WY 14,643 处理会增加肝脏、肾脏和小肠中 MCT1 的 mRNA 浓度，而在 PPARα 基因敲除小鼠中未观察到上调现象。
