Dataset Information

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis.

ABSTRACT: Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FLII) and leucine-rich-repeat-(in FLII)-interacting-protein-1 as a regulatory complex for UCP1 transcription. Physiologically, FGF6/9 expression in adipose is upregulated by exercise and cold in mice, and FGF9/FGFR3 expression in human neck fat is significantly associated with UCP1 expression. Loss of FGF9 impairs BAT thermogenesis. In vivo administration of FGF9 increases UCP1 expression and thermogenic capacity. Thus, FGF6 and FGF9 are adipokines that can regulate UCP1 through a transcriptional network that is dissociated from brown adipogenesis, and act to modulate systemic energy metabolism.

SUBMITTER: Shamsi F

PROVIDER: S-EPMC7078224 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis.

Shamsi Farnaz F Xue Ruidan R Huang Tian Lian TL Lundh Morten M Liu Yang Y Leiria Luiz O LO Lynes Matthew D MD Kempf Elena E Wang Chih-Hao CH Sugimoto Satoru S Nigro Pasquale P Landgraf Kathrin K Schulz Tim T Li Yiming Y Emanuelli Brice B Kothakota Srinivas S Williams Lewis T LT Jessen Niels N Pedersen Steen Bønløkke SB Böttcher Yvonne Y Blüher Matthias M Körner Antje A Goodyear Laurie J LJ Mohammadi Moosa M Kahn C Ronald CR Tseng Yu-Hua YH

Nature communications 20200317 1

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FL ...[more]

PMID: 32184391

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Project description:Brown adipose tissue (BAT) is specialized for energy expenditure, thus a better understanding of the regulators influencing BAT development could provide novel strategies to defense obesity. Many protein-coding genes, miRNAs, and lncRNAs have been investigated in BAT development, however, the expression patterns and functions of circRNA in brown adipogenesis have not been reported yet. This study determined the circRNA expression profiles across brown adipogenesis (proliferation, early differentiated, and fully differentiated stages) by RNA-seq. We identified 3,869 circRNAs and 36.9% of them were novel. We found the biogenesis of circRNA was significantly related to linear mRNA transcription, meanwhile, almost 70% of circRNAs were generated by alternative back-splicing. Next, we examined the cell-specific and differentiation stage-specific expression of circRNAs. Compared to white adipocytes, nearly 30% of them were specifically expressed in brown adipocytes. Further, time-series expression analysis showed circRNAs were dynamically expressed, and 117 differential expression circRNAs (DECs) in brown adipogenesis were identified, with 77 upregulated and 40 downregulated. Experimental validation showed the identified circRNAs could be successfully amplified and the expression levels detected by RNA-seq were reliable. For the potential functions of the circRNAs, GO analysis suggested that the decreased circRNAs were enriched in cell proliferation terms, while the increased circRNAs were enriched in development and thermogenic terms. Bioinformatics predictions showed that DECs contained numerous binding sites of functional miRNAs. More interestingly, most of the circRNAs contained multiple binding sites for the same miRNA, indicating that they may facilitate functions by acting as microRNA sponges. Collectively, we characterized the circRNA expression profiles during brown adipogenesis and provide numerous novel circRNAs candidates for future brown adipogenesis regulating studies.

Dataset Information

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis.

Publications

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis.

Similar Datasets

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