iScience · 10 authors, 6 centres
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This study created a public database called FATTLAS for analyzing mouse and human adipose tissue RNA-seq data and used it to identify GPCRs with altered expression in obesity. Functional experiments in a mouse (pre)adipocyte cell line demonstrated that four newly implicated GPCRs (GPR146, MRGPRF, FZD5, PTGER2) are involved in adipogenesis, with GPR146 also regulating lipolysis.
The study established FATTLAS, an interactive database for analyzing publicly available RNA-seq data from mouse and human adipose tissue. Researchers used the database to identify highly expressed and differentially regulated G protein-coupled receptors (GPCRs) in non-obese versus obese individuals. Four candidate GPCRs—GPR146, MRGPRF, FZD5, and PTGER2—were selected for functional validation using siRNA knockdown in the 3T3-L1 (pre)adipocyte cell line. All four receptors were found to be involved in adipogenesis. Specifically, MRGPRF knockdown reduced lipid accumulation and cAMP levels, FZD5 knockdown impaired preadipocyte viability and lipid accumulation, PTGER2 knockdown affected lipid droplet growth, and GPR146 knockdown reduced adipogenesis and increased lipolysis. Key limitations include the use of a mouse cell line, the inability to test receptor activation due to missing agonists, and the indirect nature of human relevance derived from reanalyzing adipose tissue rather than adipocyte RNA-seq data.
