Hypoxia-induced fatty acid transporter translocation increases fatty acid transport and contributes to lipid accumulation in the heart
Hypoxia-induced fatty acid transporter translocation increases fatty acid transport and contributes to lipid accumulation in the heart
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DOI：
10.1016/j.febslet.2006.05.045
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发表时间：
2006-06-26
期刊：
影响因子：
3.5
通讯作者：
Bonen, Arend
中科院分区：
文献类型：
--
作者：
Chabowski, Adrian;Gorski, Jan;Bonen, Arend
蛋白质介导的LCFA跨膜转运受到脂肪酸转运体FAT/CD36和FABPpm的高度调控。生理刺激(胰岛素刺激、AMP激酶激活)诱导一个或两个转运体移位到质膜，增加LCFA的转运率。在缺氧/缺血心脏中，脂肪酸氧化速率减慢可导致心肌内脂肪堆积。然而，由于急性缺氧(15分钟)激活了AMPK，我们研究了缺氧期间心肌内脂质堆积的增加是否也与AMPK诱导的脂肪/CD36和FABPpm易位导致的LCFA摄取率增加有关。在心肌细胞中，低氧(15分钟)诱导脂肪/CD36从细胞内池(LDM)(-25%，P<0.05)重新分布到质膜(PM)(+54%，P<0.05)。低氧还导致PM的FABPPM增加(+56%，P<；0.05)，伴随而来的LDM的FABPpm减少(-24%，P<；0.05)。同样，在完整的兰登多夫灌流的心脏中，低氧诱导FAT/CD36和FABPpm移位到PM(分别为+66%和+61%，P<；0.05)，伴随着LDM中FAT/CD36和FABPpm的下降(分别为-24%和-23%，P<；0.05)。重要的是，这些转运蛋白的血浆含量增加与心肌细胞摄取棕榈酸的初始速率增加(+40%，P<；0.05)相关。急性缺氧还使棕榈酸酯重定向进入细胞内脂池，主要进入细胞内脂池(+48%和+28%，P<；0.05)，而脂肪酸氧化减少(-35%，P<；0.05)。因此，我们的数据表明，低氧心脏细胞内脂质积累的增加可归因于：(A)脂肪酸氧化速率降低和(B)脂肪酸进入心脏的速率增加，后者可归因于低氧诱导的脂肪酸转运体的移位。(C)2006年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Protein-mediated LCFA transport across plasma membranes is highly regulated by the fatty acid transporters FAT/CD36 and FABPpm. Physiologic stimuli (insulin stimulation, AMP kinase activation) induce the translocation of one or both transporters to the plasma membrane and increase the rate of LCFA transport. In the hypoxic/ischemic heart, intramyocardial lipid accumulation has been attributed to a reduced rate of fatty acid oxidation. However, since acute hypoxia (15 min) activates AMPK, we examined whether an increased accumulation of intramyocardial lipid during hypoxia was also attributable to an increased rate of LCFA uptake as a result AMPK-induced translocation of FAT/CD36 and FABPpm. In cardiac myocytes, hypoxia (15 min) induced the redistribution of FAT/CD36 from an intracellular pool (LDM) (-25%, P < 0.05) to the plasma membranes (PM) (+54%, P < 0.05). Hypoxia also induced an increase in FABPpm at the PM (+56%, P < 0.05) and a concomitant FABPpm reduction in the LDM (-24%, P < 0.05). Similarly, in intact, Langendorff perfused hearts, hypoxia induced the translocation of a both FAT/ CD36 and FABPpm to the PM (+66% and +61%, respectively, P < 0.05), with a concomitant decline in FAT/CD36 and FABPpm in the LDM (-24% and -23%, respectively, P < 0.05). Importantly, the increased plasmalemmal content of these transporters was associated with increases in the initial rates of palmitate uptake into cardiac myocytes (+40%, P < 0.05). Acute hypoxia also redirected palmitate into intracellular lipid pools, mainly to PL and TG (+48% and +28%, respectively, P < 0.05), while fatty acid oxidation was reduced (-35%, P < 0.05). Thus, our data indicate that the increased intracellular lipid accumulation in hypoxic hearts is attributable to both: (a) a reduced rate of fatty acid oxidation and (b) an increased rate of fatty acid transport into the heart, the latter being attributable to a hypoxia-induced translocation of fatty acid transporters. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.