Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling.
Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling.
复制标题
DOI：
10.1016/j.plipres.2013.04.001
复制
发表时间：
2013-07
影响因子：
13.6
通讯作者：
Reue K
中科院分区：
文献类型：
--
作者：
Csaki LS;Dwyer JR;Fong LG;Tontonoz P;Young SG;Reue K
脂蛋白家族成员是磷脂酸磷酸酶（PAP），它催化磷脂酸去磷酸化生成二酰甘油，这是甘油三酯（TAG）合成的倒数第二步。脂蛋白在甘油脂生物合成酶中是独特的，因为它们还通过作为与DNA结合的转录因子的共调节因子来调节基因表达，从而促进脂肪酸氧化。从酵母中的单个直系同源物到哺乳动物的三种脂蛋白——脂蛋白 -1、脂蛋白 -2和脂蛋白 -3家族，脂蛋白的功能在进化上是保守的。在小鼠和人类中，脂蛋白活性水平是多种细胞类型中甘油三酯储存的决定因素，脂蛋白 -1或脂蛋白 -2缺乏的人患有严重的代谢疾病。最近的研究强调了脂蛋白家族成员之间复杂的生理相互作用，它们在特定组织中表现出重叠和独特的功能。对小鼠模型和人类中“脂蛋白病”的分析揭示了脂蛋白活性在调节脂质中间产物（磷脂酸和二酰甘油）方面的重要作用，这些脂质中间产物影响基本的细胞过程，包括脂肪细胞和神经细胞分化、脂肪细胞脂解以及肝脏胰岛素信号传导。对脂蛋白分子和生理功能的阐明可能会带来调节细胞脂质储存和代谢疾病的新方法。
Members of the lipin protein family are phosphatidate phosphatase (PAP) enzymes, which catalyze the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in TAG synthesis. Lipins are unique among the glycerolipid biosynthetic enzymes in that they also promote fatty acid oxidation through their activity as co-regulators of gene expression by DNA-bound transcription factors. Lipin function has been evolutionarily conserved from a single ortholog in yeast to the mammalian family of three lipin proteins—lipin-1, lipin-2, and lipin-3. In mice and humans, the levels of lipin activity are a determinant of TAG storage in diverse cell types, and humans with deficiency in lipin-1 or lipin-2 have severe metabolic diseases. Recent work has highlighted the complex physiological interactions between members of the lipin protein family, which exhibit both overlapping and unique functions in specific tissues. The analysis of “lipinopathies” in mouse models and in humans has revealed an important role for lipin activity in the regulation of lipid intermediates (phosphatidate and diacylglycerol), which influence fundamental cellular processes including adipocyte and nerve cell differentiation, adipocyte lipolysis, and hepatic insulin signaling. The elucidation of lipin molecular and physiological functions could lead to novel approaches to modulate cellular lipid storage and metabolic disease.
登录
查看更多内容
评估英国种群中LPIN1变异在胰岛素抵抗，体重和人脂肪营养不良中的作用。
影响因子：
7.7
作者：
Fawcett KA;Grimsey N;Loos RJ;Wheeler E;Daly A;Soos M;Semple R;Syddall H;Cooper C;Siniossoglou S;O'Rahilly S;Wareham NJ;Barroso I
通讯作者：
Barroso I
影响因子：
5.8
作者：
Donkor, Jimmy;Sparks, Lauren M.;Reue, Karen
通讯作者：
Reue, Karen
影响因子：
4
作者：
Ferguson, PJ;Chen, S;El-Shanti, H
通讯作者：
El-Shanti, H
影响因子：
4.8
作者：
Fakas, Stylianos;Qiu, Yixuan;Carman, George M.
通讯作者：
Carman, George M.
影响因子：
4.8
作者：
Donkor, Jimmy;Sariahmetoglu, Meltem;Reue, Karen
通讯作者：
Reue, Karen