Fibroblast growth factors induce preadipocyte UCP1 expression and imprint on post-differentiation white and brown adipocyte function

Objective: 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. Methods: 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. Results: 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 protein abundance or 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. Conclusion: Thus, FGF-induced Ucp1 expression in preadipocytes programs a lasting post-differentiation anti-inflammatory status. Overall design: Following primary preadipocyte isolation (stromal vascular fraction) from iBAT and iWAT (C57BL/6N, wild-type), cells were treated upon confluency with 5.5 nM FGF2 or let untreated for 48 hours.