PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation.
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation.
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DOI：
10.3390/ijms19113447
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发表时间：
2018-11-02
影响因子：
5.6
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Cheng CF;Ku HC;Lin H
过氧化物酶体增殖物激活受体γ辅活化子1α(PGC-1α)是一种91 kDa的转录因子，它通过上调三羧酸循环和线粒体脂肪酸氧化途径中几个基因的表达来调节脂代谢和长链脂肪酸氧化。此外，pGC-1α还调节线粒体基因的表达，从而控制线粒体的复制和细胞的氧化代谢。最近，新的研究发现，在骨骼肌中，几种肌肉运动因子，如淫羊藿素和肌肉生长抑素，受前列腺素C-1α的表观遗传调控，从而调节全身能量平衡，使健康或疾病心肌的线粒体体密度和氧化能力显著扩大。此外，在评价心外膜脂肪组织中PGC-1α的过表达是否可以作为旁分泌器官改善或修复心功能时，我们发现在体内和体外，肝脏PGC-1α的过表达增加了肝脏脂肪酸的氧化，减少了三酰甘油的储存和分泌。在本文中，我们讨论了最近的研究表明，在急、慢性肾损伤中，前列腺素C-1α可能调节线粒体融合-分裂动态平衡，影响肾功能。此外，pGC-1α是一种新出现的蛋白质，在癌症中具有双相作用，既是肿瘤抑制因子，又是肿瘤促进剂，是癌症生物学研究中一个新的、尚未解决的课题。综上所述，这篇综述文章表明，pGC-1α在协调线粒体生物发生的关键组成部分的基因表达中发挥着核心作用，并作为许多重要器官的关键代谢调节因子，包括白色和棕色脂肪组织、骨骼肌、心脏、肝脏和肾脏。
Traditionally, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a 91 kDa transcription factor, regulates lipid metabolism and long-chain fatty acid oxidation by upregulating the expression of several genes of the tricarboxylic acid cycle and the mitochondrial fatty acid oxidation pathway. In addition, PGC-1α regulates the expression of mitochondrial genes to control mitochondria DNA replication and cellular oxidative metabolism. Recently, new insights showed that several myokines such as irisin and myostatin are epigenetically regulated by PGC-1α in skeletal muscles, thereby modulating systemic energy balance, with marked expansion of mitochondrial volume density and oxidative capacity in healthy or diseased myocardia. In addition, in our studies evaluating whether PGC-1α overexpression in epicardial adipose tissue can act as a paracrine organ to improve or repair cardiac function, we found that overexpression of hepatic PGC-1α increased hepatic fatty acid oxidation and decreased triacylglycerol storage and secretion in vivo and in vitro. In this review, we discuss recent studies showing that PGC-1α may regulate mitochondrial fusion–fission homeostasis and affect the renal function in acute or chronic kidney injury. Furthermore, PGC-1α is an emerging protein with a biphasic role in cancer, acting both as a tumor suppressor and a tumor promoter and thus representing a new and unresolved topic for cancer biology studies. In summary, this review paper demonstrates that PGC-1α plays a central role in coordinating the gene expression of key components of mitochondrial biogenesis and as a critical metabolic regulator in many vital organs, including white and brown adipose tissue, skeletal muscle, heart, liver, and kidney.
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DOI：
10.1073/pnas.0603615103
发表时间：
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影响因子：
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影响因子：
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