Ishimoto Kenji
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Yakugaku Zasshi. 2011;131(8):1189-94. doi: 10.1248/yakushi.131.1189.
The gene encoding lipin 1 was identified with a positional cloning approach that localized the causative mutation in fatty liver dystrophic (fld) mice, a mouse model of lipodystrophy. The fld mouse lacks normal adipose tissue in the body, and displays metabolic dysregulation such as obesity, insulin resistance, and hypertriglyceridemia. Lipin 1 is abundantly expressed in key metabolic tissues, including adipose tissue, skeletal muscle, and liver. In the cytosol, lipin 1 acts as an Mg²⁺-dependent phosphatidate phosphatase type-1 (PAP1), catalyzing a key step in the synthesis of glycerolipids. In the nucleus, lipin 1 acts as a transcriptional coactivator through its direct interaction with peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α) and PPARα. Through two distinct functions in the nucleus and cytosol, lipin 1 modulates lipid metabolism and glucose homeostasis. Here we will discuss recent developments in our understanding of the role of lipin 1 in lipid metabolism.
编码脂联素1的基因是通过定位克隆方法鉴定出来的，该方法将致病变异定位在脂肪性肝营养不良（fld）小鼠中，这是一种脂肪营养不良的小鼠模型。fld小鼠体内缺乏正常的脂肪组织，并表现出代谢失调，如肥胖、胰岛素抵抗和高甘油三酯血症。脂联素1在关键代谢组织中大量表达，包括脂肪组织、骨骼肌和肝脏。在细胞质中，脂联素1作为一种镁离子依赖性磷脂酸磷酸酶1型（PAP1），催化甘油olipids合成中的关键步骤。在细胞核中，脂联素1通过与过氧化物酶体增殖物激活受体（PPAR）γ共激活因子-1α（PGC-1α）和PPARα直接相互作用，作为转录共激活因子。通过在细胞核和细胞质中的两种不同功能，脂联素1调节脂质代谢和葡萄糖稳态。在这里，我们将讨论我们对脂联素1在脂质代谢中作用的理解的最新进展。
