Leptin regulates energy metabolism in MCF-7 breast cancer cells
Leptin regulates energy metabolism in MCF-7 breast cancer cells
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DOI：
10.1016/j.biocel.2016.01.002
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发表时间：
2016-03-01
影响因子：
4
通讯作者：
Roca, Pilar
中科院分区：
文献类型：
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作者：
del Mar Blanquer-Rossello, Ma;Oliver, Jordi;Roca, Pilar
众所周知，肥胖是绝经后女性患乳腺癌的一个较差的预后因素。在与肥胖相关的多种内分泌因素中，瘦素受到了特别的关注，因为它促进了乳腺癌细胞的生长和侵袭性，迫使细胞调整自己的新陈代谢，以满足日益增长的能量和生物合成中间体的需求。考虑到这一点，我们的目的是探讨瘦素在MCF-7乳腺癌细胞代谢中的作用。极谱分析显示，与糖酵解更多的对照细胞相比，瘦素处理的细胞增加了耗氧率，细胞内的ATP水平更依赖于线粒体的氧化代谢。用糖酵解(2-DG)、脂肪酸氧化(Etomoxir)或氨基酸剥夺的选择性抑制剂进行的实验表明，ATP水平更依赖于脂肪酸氧化。与此一致的是，瘦素增加了参与脂质分解代谢的关键蛋白(脂肪/CD36、CPT1、PPARα)和能量感受器AMPK的磷酸化水平。至于葡萄糖，细胞摄取不受瘦素的影响，但乳酸的释放受到严重抑制。丙酮酸脱氢酶(PDH)、乳酸脱氢酶(LDH)、丙酮酸羧化酶(PC)以及磷酸戊糖途径酶葡萄糖-6磷酸脱氢酶(G6PDH)的分析表明，瘦素有利于利用葡萄糖进行生物合成。这些结果表明瘦素在代谢重新编程中的作用，包括加强葡萄糖用于生物合成和脂类用于能量生产。瘦素诱导的这种代谢适应可能有利于MCF-7的生长，并支持乳腺癌中描述的反向Warburg效应。(C)2016爱思唯尔有限公司。保留所有权利。
Obesity is known to be a poorer prognosis factor for breast cancer in postmenopausal women. Among the diverse endocrine factors associated to obesity, leptin has received special attention since it promotes breast cancer cell growth and invasiveness, processes which force cells to adapt their metabolism to satisfy the increased demands of energy and biosynthetic intermediates. Taking this into account, our aim was to explore the effects of leptin in the metabolism of MCF-7 breast cancer cells. Polarographic analysis revealed that leptin increased oxygen consumption rate and cellular ATP levels were more dependent on mitochondrial oxidative metabolism in leptin-treated cells compared to the more glycolytic control cells. Experiments with selective inhibitors of glycolysis (2-DG), fatty acid oxidation (etomoxir) or aminoacid deprivation showed that ATP levels were more reliant on fatty acid oxidation. In agreement, levels of key proteins involved in lipid catabolism (FAT/CD36, CPT1, PPAR alpha) and phosphorylation of the energy sensor AMPK were increased by leptin. Regarding glucose, cellular uptake was not affected by leptin, but lactate release was deeply repressed. Analysis of pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH) and pyruvate carboxylase (PC) together with the pentose-phosphate pathway enzyme glucose-6 phoshate dehydrogenase (G6PDH) revealed that leptin favors the use of glucose for biosynthesis. These results point towards a role of leptin in metabolic reprogramming, consisting of an enhanced use of glucose for biosynthesis and lipids for energy production. This metabolic adaptations induced by leptin may provide benefits for MCF-7 growth and give support to the reverse Warburg effect described in breast cancer. (C) 2016 Elsevier Ltd. All rights reserved.