Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells
Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells
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DOI：
10.1016/j.biocel.2012.07.026
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发表时间：
2012-11-01
影响因子：
4
通讯作者：
Palou, Andreu
中科院分区：
文献类型：
--
作者：
Amengual, Jaume;Petrov, Petar;Palou, Andreu
维生素A衍生物视黄酸（RA）是哺乳动物肥胖和脂质代谢的重要调节剂，主要通过RA受体（RAR）和类维生素A X受体（RXR）亚家族的核受体在基因表达水平起作用。在这里，我们研究了RA对脂肪酸代谢，特别是脂肪酸氧化，在人肝癌HepG 2细胞的细胞自主作用。全反式维甲酸（ATRA）暴露于剂量和时间依赖性方式上调肉毒碱棕榈酰转移酶-1（CPT 1-L）在HepG 2细胞中的表达，并增加外源性添加的放射性标记棕榈酸的细胞氧化速率。ATRA对CPT 1-L基因表达的影响是：依赖于正在进行的转录，由9-cis RA和pan-RXR激动剂（但不是pan-RAR激动剂）复制，并在RXR alpha部分siRNA介导的沉默后消除。CPT 1-L基因表达在HepG 2细胞中协同诱导，同时暴露于ATRA和选择性过氧化物酶体增殖物激活受体α激动剂。我们的结论是，ATRA治疗增强脂肪酸catalysts在肝细胞通过RXR介导的机制，可能涉及的PPAR α：RXR异源二聚体的反式激活。了解能够全身性和特异性增强肝脏底物氧化的试剂和营养衍生物及其作用机制，可能有助于预防和治疗脂肪肝、肥胖症和其他代谢综合征相关疾病的新途径。(c)2012爱思唯尔有限公司保留所有权利。
The vitamin A derivative retinoic acid (RA) is an important regulator of mammalian adiposity and lipid metabolism, primarily acting at the gene expression level through nuclear receptors of the RA receptor (RAR) and retinoid X receptor (RXR) subfamilies. Here, we studied cell-autonomous effects of RA on fatty acid metabolism, particularly fatty acid oxidation, in human hepatoma HepG2 cells. Exposure to all-trans RA (ATRA) up-regulated the expression of carnitine palmitoyl transferase-1 (CPT1-L) in HepG2 cells in a dose- and time-dependent manner, and increased cellular oxidation rate of exogenously added radiolabeled palmitate. The effect of ATRA on gene expression of CPT1-L was: dependent on ongoing transcription, reproduced by both 9-cis RA and a pan-RXR agonist (but not a pan-RAR agonist) and abolished following RXR alpha partial siRNA-mediated silencing. CPT1-L gene expression was synergistically induced in HepG2 cells simultaneously exposed to ATRA and a selective peroxisome proliferator-activated receptor alpha agonist. We conclude that ATRA treatment enhances fatty acid catabolism in hepatocytes through RXR-mediated mechanisms that likely involve the transactivation of the PPAR alpha:RXR heterodimer. Knowledge of agents and nutrient-derivatives capable of enhancing substrate oxidation systemically and specifically in liver, and their mechanisms of action, may contribute to new avenues of prevention and treatment of fatty liver, obesity and other metabolic syndrome-related disorders. (c) 2012 Elsevier Ltd. All rights reserved.