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Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.

Authors: Qiu, Yifu  Nguyen, Khoa D  Odegaard, Justin I  Cui, Xiaojin  Tian, Xiaoyu  Locksley, Richard M  Palmiter, Richard D  Chawla, Ajay 
Citation: Qiu Y, etal., Cell. 2014 Jun 5;157(6):1292-308. doi: 10.1016/j.cell.2014.03.066.
Pubmed: (View Article at PubMed) PMID:24906148
DOI: Full-text: DOI:10.1016/j.cell.2014.03.066

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.

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RGD Object Information
RGD ID: 13673787
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.