Kaczmarek Isabell, Wower Isabel, Ettig Katja, Kuhn Christina Katharina, Kraft Robert, Landgraf Kathrin, Körner Antje, Schöneberg Torsten, Horn Susanne, Thor Doreen
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
Carl Ludwig Institute for Physiology, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
iScience. 2023 Sep 9;26(10):107841. doi: 10.1016/j.isci.2023.107841. eCollection 2023 Oct 20.
G protein-coupled receptors (GPCRs) modulate the function of adipose tissue (AT) in general and of adipocytes, specifically. Although it is well-established that GPCRs are widely expressed in AT, their repertoire as well as their regulation and function in (patho)physiological conditions (e.g., obesity) is not fully resolved. Here, we established FATTLAS, an interactive public database, for improved access and analysis of RNA-seq data of mouse and human AT. After extracting the GPCRome of non-obese and obese individuals, highly expressed and differentially regulated GPCRs were identified. Exemplarily, we describe four receptors (GPR146, MRGPRF, FZD5, PTGER2) and analyzed their functions in a (pre)adipocyte cell model. Besides all receptors being involved in adipogenesis, MRGPRF is essential for adipocyte viability and regulates cAMP levels, while GPR146 modulates adipocyte lipolysis via constitutive activation of Gi proteins. Taken together, by implementing and using FATTLAS we describe four hitherto unrecognized GPCRs associated with AT function and adipogenesis.
G蛋白偶联受体(GPCRs)总体上调节脂肪组织(AT)的功能,具体而言调节脂肪细胞的功能。尽管GPCRs在脂肪组织中广泛表达已得到充分证实,但其种类以及在(病理)生理条件(如肥胖)下的调节和功能尚未完全明确。在此,我们建立了FATTLAS,一个交互式公共数据库,以改善对小鼠和人类脂肪组织RNA测序数据的访问和分析。在提取非肥胖和肥胖个体的GPCR组后,鉴定出高表达和差异调节的GPCRs。例如,我们描述了四种受体(GPR146、MRGPRF、FZD5、PTGER2),并在(前)脂肪细胞模型中分析了它们的功能。除了所有受体都参与脂肪生成外,MRGPRF对脂肪细胞活力至关重要并调节cAMP水平,而GPR146通过Gi蛋白的组成性激活调节脂肪细胞脂解。总之,通过实施和使用FATTLAS,我们描述了四种迄今未被认识的与脂肪组织功能和脂肪生成相关的GPCRs。