Expression of APOD regulated by NR1H2 or NR1H3

The apolipoprotein D (APOD) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. APOD is an atypical apolipoprotein that belongs to the lipocalin family, and is expressed by a wide variety of cells and tissues (Drayna D et al. 1986). The liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) were found to regulate the expression of the APOD gene in cultured cells and in vivo (Hummasti S et al. 2004; Lai C-J et al. 2017). Synthetic LXR agonist treatment of mouse adipocytes (3T3-L1 cells) and human umbilical vein endothelial cells (HUVECs) resulted in increased mRNA and protein levels of APOD (Hummasti S et al. 2004; Lai C-J et al. 2017). An LXR response element (LXRE) was identified in the human APOD gene promoter, and binding of LXRα (NR1H3):RXRa heterodimers was demonstrated by electrophoretic mobility shift assay (EMSA) and luciferase cell reporter assay (Hummasti S et al. 2004). Mice treated with synthetic LXR agonists exhibited increased APOD mRNA levels in adipose tissue, skeletal muscle and cerebellum, but not liver (Hummasti S et al. 2004; Repa JJ et al. 2007). In humans, APOD is found in the plamsa, associated with high-density lipoprotein (HDL), and polymorphisms have been linked to metabolic disease. APOD has also been suggested to be neuroprotective (Pascua-Maestro R et al 2019).

脂蛋白D（APOD）基因通过转录生成信使RNA（mRNA），进而翻译成蛋白质。APOD作为一种非典型的脂蛋白，隶属于脂蛋白家族，并在多种细胞和组织中表达（Drayna D et al. 1986）。肝脏X受体α（LXRα，NR1H3）和LXRβ（NR1H2）被发现能够调节APOD基因在培养细胞及体内的表达（Hummasti S et al. 2004；Lai C-J et al. 2017）。对小鼠脂肪细胞（3T3-L1细胞）和人类脐静脉内皮细胞（HUVECs）进行合成的LXR激动剂处理，导致APOD mRNA和蛋白质水平上升（Hummasti S et al. 2004；Lai C-J et al. 2017）。在人类APOD基因启动子中鉴定出LXR反应元件（LXRE），并通过电泳迁移率变动分析（EMSA）和荧光素酶细胞报告基因分析（Hummasti S et al. 2004）证实了LXRα（NR1H3）：RXRa异源二聚体的结合。接受合成LXR激动剂治疗的鼠类，其脂肪组织、骨骼肌和小脑中的APOD mRNA水平升高，但肝脏中并未升高（Hummasti S et al. 2004；Repa JJ et al. 2007）。在人类中，APOD存在于血浆中，与高密度脂蛋白（HDL）相关联，且多态性与代谢性疾病有关。APOD还被认为具有神经保护作用（Pascua-Maestro R et al 2019）。