Preadipocyte uncoupling protein 1 expression invoked by fibroblast growth factors imprints on post-differentiation white and brown adipocyte function [2]

The presence of uncoupling protein 1 (UCP1) is a hallmark of thermogenic adipocytes and enables heat production by dissipating energy from mitochondrial proton motive force as heat. The purpose of its recently discovered presence in preadipocytes in response to certain fibroblast growth factors (FGFs) remains elusive. In this study, we systematically investigated the potential of all paracrine FGFs to invoke Ucp1 expression in murine preadipocytes derived from interscapular brown and inguinal white adipose tissue. The factors FGF2, FGF4, FGF8, and FGF9 induced Ucp1 expression in undifferentiated preadipocytes, with FGF2 acting most potently and rapidly. This premature Ucp1 induction did not translate into increased Ucp1 thermogenic activity after full adipogenic differentiation. Notably, preadipocyte treatment with FGFs and parallel Ucp1 expression led to a sustained suppression of interferon-stimulated genes after differentiation. Preadipocyte Ucp1 was required and sufficient for this lasting imprint. Thus, FGF-induced Ucp1 expression in preadipocytes programs a lasting post-differentiation anti-inflammatory status. Overall design: Stromal vascular fraction (SVF) cells were isolated from interscapular brown adipose tissue (iBAT) of C57BL/6N wild-type and Ucp1 knockout mice. Cells were cultured to 70–80% confluency and treated at the preadipocyte stage with either 5.5 nM FGF2, 250 nM of the FGFR inhibitor LY (LY2874455), or left untreated for 48 hours. Subsequently, differentiation into mature brown adipocytes was induced (Gantert et al. 2021). Total mRNA was extracted using the SV Total RNA Isolation System (Promega). For each condition, mRNA from three biological replicates was pooled prior to library preparation and sequencing, which were performed by Novogene.