C.L. and M.M. contributed equally to this work.

The de novo differentiation of hyperplastic adipocytes from adipocyte progenitor cells (APCs) is accompanied by the reduction of adipose tissue fibrosis and inflammation and improvement in insulin sensitivity in obesity and aging. However, the regulators of APC proliferation are poorly understood. Here, we show that fibroblast growth factor 6 (FGF6) secreted by adipocytes controls PDGFRa+ APC proliferation via extracellular signal-regulated kinase (ERK) signaling. Specific FGF6 overexpression in inguinal white adipose tissue (iWAT) improved the signs of high-fat diet- or aging-induced adipose hypertrophy 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.

This article contains supplementary material online at https://doi.org/10.2337/figshare.21816033.

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