Identifying G protein-coupled receptors involved in adipose tissue function using the innovative RNA-seq database FATTLAS

Isabell Kaczmarek; Isabel Wower; Katja Ettig; Christina Katharina Kuhn; Robert Kraft; Kathrin Landgraf; Antje Körner; Torsten Schöneberg; Susanne Horn; Doreen Thor

doi:10.1016/j.isci.2023.107841

Identifying G protein-coupled receptors involved in adipose tissue function using the innovative RNA-seq database FATTLAS

iScience. 2023 Sep 9;26(10):107841. doi: 10.1016/j.isci.2023.107841. eCollection 2023 Oct 20.

Authors

Isabell Kaczmarek¹, Isabel Wower¹, Katja Ettig¹, Christina Katharina Kuhn¹, Robert Kraft², Kathrin Landgraf³, Antje Körner^{3

4}, Torsten Schöneberg^{1

5}, Susanne Horn^{1

6}, Doreen Thor¹

Affiliations

¹ Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
² Carl Ludwig Institute for Physiology, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
³ Center for Pediatric Research Leipzig, Hospital for Children & Adolescents, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
⁴ Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany.
⁵ School of Medicine, University of Global Health Equity (UGHE), Kigali, Rwanda.
⁶ Department of Dermatology, University Hospital Essen, University Duisburg-Essen, and German Cancer Consortium (DKTK) partner site Essen/Düsseldorf, 45122 Essen, Germany.

Abstract

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.

Keywords: Bioinformatics; Biological sciences; Molecular biology; Natural sciences; Physiology.