The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity

Zhe Huang, Ling Zhong, Jimmy Tsz Hang Lee, Jialiang Zhang, Donghai Wu, Leiluo Geng, Yu Wang, Chi Ming Wong, Aimin Xu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

48 Citations (Scopus)

Abstract

Type 2 cytokines are important signals triggering biogenesis of thermogenic beige adipocytes in white adipose tissue (WAT) during cold acclimation. However, how cold activates type 2 immunity in WAT remains obscure. Here we show that cold-induced type 2 immune responses and beiging in subcutaneous WAT (scWAT) are abrogated in mice with adipose-selective ablation of FGF21 or its co-receptor β-Klotho, whereas such impairments are reversed by replenishment with chemokine CCL11. Mechanistically, FGF21 acts on adipocytes in an autocrine manner to promote the expression and secretion of CCL11 via activation of ERK1/2, which drives recruitment of eosinophils into scWAT, leading to increases in accumulation of M2 macrophages, and proliferation and commitment of adipocyte precursors into beige adipocytes. These FGF21-elicited type 2 immune responses and beiging are blocked by CCL11 neutralization. Thus, the adipose-derived FGF21-CCL11 axis triggers cold-induced beiging and thermogenesis by coupling sympathetic nervous system to activation of type 2 immunity in scWAT. Zhe Huang et al. show that cold activates type 2 immune responses and beiging in subcutaneous WAT through an FGF21-CCL11 axis which drives eosinophil recruitment, M2 macrophage accumulation and proliferation and commitment of beige adipocyte precursors. These findings explain how the immune system communicates with sympathetic nerves to control adaptive thermogenesis.
Original languageEnglish
Pages (from-to)493-508.e4
JournalCell Metabolism
Volume26
Issue number3
DOIs
Publication statusPublished - 5 Sep 2017
Externally publishedYes

Keywords

  • adaptive thermogenesis
  • adipocyte precursor cells
  • adipose remodeling
  • beiging
  • eosinophils
  • eotaxin
  • macrophages
  • type 2 immunity

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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