Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.
Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.
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DOI：
10.1016/j.cell.2014.03.066
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发表时间：
2014-06-05
期刊：
影响因子：
64.5
通讯作者：
Chawla A
中科院分区：
文献类型：
--
作者：
Qiu Y;Nguyen KD;Odegaard JI;Cui X;Tian X;Locksley RM;Palmiter RD;Chawla A
米色脂肪表达产热蛋白UCP1，可以抵御寒冷和肥胖。尽管寒冷环境是小鼠和人类诱导米色脂肪的生理刺激，但从感知寒冷到米色脂肪形成的过程仍然知之甚少。在这里，我们确定了传出米色脂肪产热回路，由嗜酸性粒细胞、2型细胞因子白介素(IL)-4/13和交替活化的巨噬细胞组成。嗜酸性粒细胞或IL-4/13信号的遗传缺失会损害冷诱导的米色脂肪的生物发生。在机制上，被招募到冷应激下皮下白色脂肪组织（scWAT）的巨噬细胞通过选择性激活来诱导酪氨酸羟化酶的表达和儿茶酚胺的产生，这是scWAT褐变所需的因子。相反，给热中性小鼠注射IL-4会增加米色脂肪量和产热能力，从而改善预先建立的肥胖。总之，我们的发现揭示了控制米色脂肪生物发生的传出回路，并为其靶向治疗肥胖提供了支持。
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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影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
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影响因子：
64.5
作者：
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通讯作者：
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