Cell
Volume 157, Issue 6, 5 June 2014, Pages 1292-1308
Journal home page for Cell

Article
Eosinophils and Type 2 Cytokine Signaling in Macrophages Orchestrate Development of Functional Beige Fat

https://doi.org/10.1016/j.cell.2014.03.066Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Eosinophils and type 2 cytokines are required for biogenesis of beige fat

  • Alternatively activated macrophages support the development of functional beige fat

  • Myeloid-cell-derived catecholamines mediate the growth of cold-induced beige fat

  • IL-4 therapy increases beige fat mass to ameliorate obesity in thermoneutral mice

Summary

Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13, and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat. Mechanistically, macrophages recruited to cold-stressed subcutaneous white adipose tissue (scWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production, factors required for browning of scWAT. Conversely, administration of IL-4 to thermoneutral mice increases beige fat mass and thermogenic capacity to ameliorate pre-established obesity. Together, our findings have uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its targeting to treat obesity.

Cited by (0)