CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation

Highlights

• The chemokine CXCL14 is secreted by brown fat in response to thermogenic activation

• Brown-fat-secreted CXCL14 promotes the recruitment of M2-type macrophages

• Lack of CXCL14 impairs brown fat activity and alters glucose homeostasis

• CXCL14 induces browning of white fat via type 2 immune cells activation

Summary

The beneficial effects of brown adipose tissue (BAT) are attributed to its capacity to oxidize metabolites and produce heat, but recent data suggest that secretory properties of BAT may also be involved. Here, we identify the chemokine CXCL14 (C-X-C motif chemokine ligand-14) as a novel regulatory factor secreted by BAT in response to thermogenic activation. We found that the CXCL14 released by brown adipocytes recruited alternatively activated (M2) macrophages. Cxcl14-null mice exposed to cold showed impaired BAT activity and low recruitment of macrophages, mainly of the M2 phenotype, into BAT. CXCL14 promoted the browning of white fat and ameliorated glucose/insulin homeostasis in high-fat-diet-induced obese mice. Impairment of type 2 cytokine signaling, as seen in Stat6-null mice, blunts the action of CXCL14, promoting adipose tissue browning. We propose that active BAT is a source of CXCL14, which concertedly promotes adaptive thermogenesis via M2 macrophage recruitment, BAT activation, and the browning of white fat.