Conditional PPARγ knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function.
Conditional PPARγ knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function.
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发表时间：
2010
影响因子：
2.2
通讯作者：
Jinwen Luo;Sijie Wu;Jian Liu;Yu-quan Li;Huan Yang;Teayoun Kim;Olga Zhelyabovska;Guoliang Ding
中科院分区：
文献类型：
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作者：
Jinwen Luo;Sijie Wu;Jian Liu;Yu-quan Li;Huan Yang;Teayoun Kim;Olga Zhelyabovska;Guoliang Ding
虽然 PPARα 和 PPARδ (β) 在心肌脂质代谢转录调节中的作用已明确，但 PPARγ 在调节成人心脏脂质代谢中的重要作用仍不清楚。在本研究中，我们研究了成年小鼠基础条件下 PPARγ 是否是正常心肌脂质代谢所必需的。我们使用他莫昔芬诱导的 Cre-LoxP 介导的基因靶向策略评估了短期心肌细胞限制性 PPARγ 敲除小鼠。短期诱导后，成年小鼠心肌细胞中PPARγ mRNA和蛋白的表达显着降低。在 PPARγ 缺陷的心脏中，脂肪酸摄取和氧化中重要蛋白质的转录和蛋白质水平降低，例如 CD36、心脏型脂肪酸结合蛋白 (FABP) 和肉碱棕榈酰转移酶 I (CPT-I)。 PPARγ 缺乏的心脏中心肌脂肪酸利用率和心脏收缩均受到抑制。与对照组相比，PPARγ缺陷的心脏表现出适度的心脏肥大。这些结果表明 PPARγ 是成人心脏中基础心肌脂肪酸利用所需的转录因子。
While the roles of PPARα and PPARδ (β) in transcriptional regulation of myocardial lipid metabolisms are well established, an essential role of PPARγ in regulating lipid metabolisms in the adult heart remains unclear. In this study, we investigated whether PPARγ is required for normal myocardial lipid metabolism at basal condition in adult mice. We assessed the short-term cardiomyocyte-restricted PPARγ knockout mice with a Tamoxifen inducible Cre-LoxP mediated gene targeting strategy. The expression of PPARγ mRNA and protein in cardiomyocytes of adult mice was substantially reduced after short-term induction. Transcript and protein levels of important proteins in fatty acid uptake and oxidation, such as CD36, heart type-fatty acid binding protein (FABP), and carnitine palmitoyltransferase I (CPT-I) were reduced in the PPARγ deficient hearts. Myocardial fatty acid utilization and cardiac contraction were depressed in PPARγ deficient hearts. The PPARγ deficient hearts exhibited modest cardiac hypertrophy compared with controls. These results indicate that PPARγ is a transcription factor that is required for basal myocardial fatty acid utilization in the adult heart.