Rac-Dependent Signaling from Keratinocytes Promotes Differentiation of Intradermal White Adipocytes

In the study, researchers investigated the role of Rac signaling in adipogenesis by creating mice with a knockout of Rac1 in keratinocytes (Rac1-KO) and a double knockout of both Rac1 and Rac3 (Rac1/Rac3-DKO). They found that Rac1-KO mice had thinner dermal white adipose tissue, which was further reduced in Rac1/Rac3-DKO mice. Analysis of primary keratinocytes from Rac1/Rac3-DKO mice showed decreased mRNA levels of several growth factors. Experiments demonstrated that a combination of BMP2 and FGF21 or BMP2 and FGF20 could induce differentiation of 3T3-L1 fibroblasts into adipocytes, an effect that was inhibited by antibodies against BMP2 or FGF21. Additionally, this combinational treatment promoted differentiation in white adipocyte precursors but not in brown adipocyte precursors, where BMP2 actually inhibited brown adipogenesis induced by FGF21. The study proposed new paracrine pathways from keratinocytes to pre-adipocytes that are Rac-dependent and modulate white adipogenesis, as well as brown adipogenesis.