PIK3CA mutations enhance the adipogenesis of ADSCs in facial infiltrating lipomatosis through TRPV1.

Facial infiltrating lipomatosis (FIL) is a congenital disorder. The pathogenesis of FIL is associated with mutations, but the underlying mechanisms remain undetermined. We found that the adipose tissue in FIL demonstrated adipocytes hypertrophy and increased lipid accumulation. All adipose-derived mesenchymal stem cells from FIL (FIL-ADSCs) harbored mutations. Moreover, FIL-ADSCs exhibited a greater capacity for adipogenesis. Knockdown of resulted in a reduction in the adipogenic potential of FIL-ADSCs. Furthermore, WX390, a dual-target PI3K/mTOR inhibitor, was found to impede -mediated adipogenesis both and . RNA sequencing (RNA-seq) revealed that the expression of transient receptor potential vanilloid subtype 1 (TRPV1) was upregulated after PI3K pathway inhibition, and overexpression or activation of TRPV1 both inhibited adipogenesis. Our study showed that mutations promoted adipogenesis in FIL-ADSCs and this effect was achieved by suppressing TPRV1. Pathogenesis experiments suggested that WX390 may serve as an agent for the treatment of FIL.