Although human dermal white adipose tissue (dWAT) envelopes scalp hair follicles (HFs), their underlying bidirectional communication remains unexplored. Recently, we determined that culturing human HFs with surrounding dWAT promoted hair growth and pigmentation ex vivo. The current study aimed to further expand knowledge of the human dWAT-HF axis.
Intriguingly, proteomic analysis identified hepatocyte growth factor (HGF) as the most abundantly-secreted dWAT product within long-term HF+dWAT ex vivo cultures. Therefore, we chose to stimulate HFs with HGF ex vivo. Both HFs cultured with dWAT, or HGF in the absence of dWAT showed a significantly increased pigment content and number of gp100+ melanocyte cells as well as maintaining higher numbers of melanocytes with three or more dendrites. These positive effects were partially ablated by a neutralizing HGF antibody added to HF+dWAT. As expected, HGF-treated HFs displayed increased proliferation and decreased apoptosis within matrix keratinocytes, effects mirrored by culturing HFs with surrounding dWAT. Transcriptomic analysis of HFs treated with HGF (6hr) revealed that HGF up-regulated PAX3 and SOX10, as well as VEGFA and WNT5B. Gene expression analysis on 24hr cultures coupled with IPA revealed that key Wnt pathway inhibitors are down-regulated in HFs treated with HGF, whereas Wnt agonists, WNT6 and WNT10B, show an upward trend for HF+HGF and HF+dWAT.   
Here we provide the first evidence that human dWAT communicates with adjacent scalp HFs by secreting HGF, one of the most potent promoters of hair growth and pigmentation. This study designates human perifollicular adipocytes and HGF-dependent dWAT-HF communication an intriguing novel target for therapeutic intervention in the future management of disorders of hair growth or pigmentation.

The role of hepatocyte growth factor in human hair follicle – dermal white adipose tissue communication