Kim Dong-Hwan, Ahn Jinsoo, Suh Yeunsu, Ziouzenkova Ouliana, Lee Jeong-Woong, Lee Kichoon
Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Department of Functional Genomics, University of Science and Technology, Daejeon, South Korea.
Front Cell Dev Biol. 2022 Apr 14;10:876031. doi: 10.3389/fcell.2022.876031. eCollection 2022.
Retinol is an essential nutrient in animals. Its metabolites, specifically retinoic acid (RA), are crucial for cell differentiation, including adipogenesis. Retinol binding protein 7 (Rbp7) is under the control of PPARγ, the master regulator of adipogenesis. However, the role of RBP7 in adipogenesis is unclear. Our study showed that Rbp7 was abundantly expressed in white and brown mouse adipose tissues and had a higher expression in adipocytes than in stromal vascular fraction. Rbp7 overexpression promoted 3T3-L1 preadipocyte differentiation with increased triglyceride accumulation and up-regulation of Pparγ, Fabp4, C/ebpα, and AdipoQ. Rbp7 deficient adipocytes had opposite effects of the overexpression, which were rescued by RA supplementation. Indirect assessment of relative nuclear RA levels using RAR response element (RARE)-Luc reporter assay demonstrated that overexpression significantly increased RARE-Luc reporter activity. Rbp7 overexpression significantly increased expression of Raldh1, responsible for RA production, and up-regulation of Lrat and Cyp26a1, involved in retinol storage and RA catabolism, respectively, in 3T3-L1 adipocytes. Rbp7 deficient adipocytes had opposite effects of the overexpression of those genes involved in retinol metabolism. These data suggest that RBP7 increases transcriptional activity of RARE that may induce negative feedback responses via regulation of the gene expression for retinol homeostasis. Our data indicate critical RBP7 functions in adipocytes: regulation of transcriptional activity of RARE and adipocytes differentiation, potentially providing a new target for obesity therapy.
视黄醇是动物体内一种必需的营养素。其代谢产物，特别是视黄酸（RA），对于包括脂肪生成在内的细胞分化至关重要。视黄醇结合蛋白7（Rbp7）受脂肪生成的主要调节因子PPARγ的控制。然而，RBP7在脂肪生成中的作用尚不清楚。我们的研究表明，Rbp7在白色和棕色小鼠脂肪组织中大量表达，且在脂肪细胞中的表达高于基质血管部分。Rbp7过表达促进3T3-L1前脂肪细胞分化，伴随着甘油三酯积累增加以及Pparγ、Fabp4、C/ebpα和AdipoQ的上调。Rbp7缺陷型脂肪细胞具有与过表达相反的作用，补充RA可使其得到挽救。使用视黄酸受体反应元件（RARE）-荧光素酶报告基因检测间接评估相对核RA水平，结果表明过表达显著增加了RARE-荧光素酶报告基因活性。Rbp7过表达显著增加了负责RA产生的Raldh1的表达，以及分别参与视黄醇储存和RA分解代谢的Lrat和Cyp26a1的上调，在3T3-L1脂肪细胞中。Rbp7缺陷型脂肪细胞对参与视黄醇代谢的那些基因的过表达具有相反的作用。这些数据表明，RBP7增加了RARE的转录活性，可能通过调节视黄醇稳态的基因表达诱导负反馈反应。我们的数据表明RBP7在脂肪细胞中具有关键功能：调节RARE的转录活性和脂肪细胞分化，可能为肥胖治疗提供一个新的靶点。
