Lipin-1 and lipin-3 together determine adiposity in vivo
Lipin-1 and lipin-3 together determine adiposity in vivo
复制标题
DOI：
10.1016/j.molmet.2013.11.008
复制
发表时间：
2014-04-01
影响因子：
8.1
通讯作者：
Reue, Karen
中科院分区：
文献类型：
--
作者：
Csaki, Lauren S.;Dwyer, Jennifer R.;Reue, Karen
磷脂酸磷酸酶的脂蛋白家族在三酰甘油合成和储存中具有确定的作用。lipin-1和lipin-2的生理作用已经被确定，但lipin-3的作用仍然是神秘的。使用lipin单敲除和双敲除模型，我们确定了lipin-3和lipin-1之间的合作关系，影响体外脂肪形成和体内肥胖。此外，100个小鼠品系中Lpin 1和Lpin 3表达水平的天然遗传变异与肥胖相关。对来自lipin单敲除和双敲除小鼠的其他代谢组织中的PAP活性的分析还揭示了lipin-1和lipin-3在脾、肾和肝中的作用，lipin-1单独在心脏和骨骼肌中的作用，以及lipin-1和lipin-2在肺和脑中的作用。我们的研究结果表明，lipin-1和lipin-3在体内合作，以确定脂肪组织PAP活性和肥胖，并可能有影响，了解保护lipin-1缺乏的人从明显的脂肪营养不良。(C)2013作者由Elsevier GmbH出版。
The lipin protein family of phosphatidate phosphatases has an established role in triacylglycerol synthesis and storage. Physiological roles for lipin-1 and lipin-2 have been identified, but the role of lipin-3 has remained mysterious. Using lipin single- and double-knockout models we identified a cooperative relationship between lipin-3 and lipin-1 that influences adipogenesis in vitro and adiposity in vivo. Furthermore, natural genetic variations in Lpin1 and Lpin3 expression levels across 100 mouse strains correlate with adiposity. Analysis of PAP activity in additional metabolic tissues from lipin single- and double-knockout mice also revealed roles for lipin-1 and lipin-3 in spleen, kidney, and liver, for lipin-1 alone in heart and skeletal muscle, and for lipin-1 and lipin-2 in lung and brain. Our findings establish that lipin-1 and lipin-3 cooperate in vivo to determine adipose tissue PAP activity and adiposity, and may have implications in understanding the protection of lipin-1-deficient humans from overt lipodystrophy. (C) 2013 The Authors. Published by Elsevier GmbH.