Fibroblast growth factor induced <i>Ucp1</i> expression in preadipocytes requires PGE2 biosynthesis and glycolytic flux

High uncoupling protein 1 (Ucp1) expression is a characteristic of differentiated brown adipocytes and linked to adipogenic differentiation. Paracrine fibroblast growth factor 8b (FGF8b) strongly induces Ucp1 transcription in white independent adipogenesis. Here, we report that FGF8b other paracrine FGFs act on preadipocytes upregulate via FGFR1-MEK1/2-ERK1/2 axis, Transcriptomic analysis revealed an upregulation prostaglandin biosynthesis glycolysis upon Fgf8b treatment preadipocytes. Oxylipin measurement by LC-MS/MS conditioned media identified E2 as putative mediator induced transcription. RNA interference pharmacological inhibition the biosynthetic pathway confirmed PGE2 causally involved control over Importantly, impairment or failure induce glycolytic flux blunted induction Ucp1, even presence PGE2. Lastly, screening factors Nrf1 Hes1 required regulators expression. Thus, conclude co-regulate glucose metabolism Nrf1/Hes1-dependent manner preadipocytes, revealing novel regulatory network formerly unrecognized cell type.