Fibroblast Growth Factor 6 Promotes Adipocyte Progenitor Cell Proliferation for Adipose Tissue Homeostasis

The de novo differentiation of hyperplastic adipocytes from adipocyte progenitor cells (APCs) is accompanied by a reduction in adipose tissue fibrosis and inflammation and improvement in insulin sensitivity in obesity and ag-ing. However, the regulators of APC proliferation are poorly understood. Here, we show that fibroblast growth factor 6 (FGF6) acts in an autocrine and/or paracrine manner to control platelet-derived growth factor receptor α–positive APC proliferation via extracellular signal–regu-lated kinase (ERK) signaling. Specific FGF6 overexpres-sion in inguinal white adipose tissue (iWAT) improved the signsofhigh-fatdiet– or aging-induced adipose hypertro-phy and insulin resistance. Conversely, chronic FGF6 expression blockade in iWAT, mediated by a neutralizing antibody or Fgf6 expression deficiency, impaired adipose tissue expansion and glucose tolerance. Overall, our data suggest that FGF6 acts as a proliferative factor for APCs to maintain fat homeostasis and insulin sensitivity.