Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling
Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling
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DOI：
10.1016/j.cmet.2016.07.023
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发表时间：
2016-09-13
期刊：
影响因子：
29
通讯作者：
Trajkovski, Mirko
中科院分区：
文献类型：
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作者：
Fabbiano, Salvatore;Suarez-Zamorano, Nicolas;Trajkovski, Mirko
热量限制（CR）延长了从酵母到哺乳动物的寿命，延迟了年龄相关疾病的发作，并改善了代谢健康。我们发现，CR刺激功能性米色脂肪的皮下和内脏脂肪组织内的发展，有助于减少白色脂肪和脂肪细胞的大小在瘦C57 BL/6和BALB/c小鼠保持在室温下或在热中性和肥胖瘦素缺乏小鼠。这些代谢变化由CR动物脂肪中嗜酸性粒细胞浸润增加、2型细胞因子信号传导和M2巨噬细胞极化介导。使用Il4ra（-/-）、Stat6（-/-）或移植有Stat6（-/-）骨髓来源的造血细胞的小鼠抑制2型信号传导，防止CR诱导的布朗宁并消除CR诱导的皮下脂肪损失和代谢改善。这些结果为CR期间的整体能量稳态提供了见解，并且它们表明米色脂肪发育是负能量平衡条件下的常见特征。
Caloric restriction (CR) extends lifespan from yeast to mammals, delays onset of age-associated diseases, and improves metabolic health. We show that CR stimulates development of functional beige fat within the subcutaneous and visceral adipose tissue, contributing to decreased white fat and adipocyte size in lean C57BL/6 and BALB/c mice kept at room temperature or at thermoneutrality and in obese leptin-deficient mice. These metabolic changes are mediated by increased eosinophil infiltration, type 2 cytokine signaling, and M2 macrophage polarization in fat of CR animals. Suppression of the type 2 signaling, using Il4ra(-/-), Stat6(-/-), or mice transplanted with Stat6(-/-) bone marrow-derived hematopoietic cells, prevents the CR-induced browning and abrogates the subcutaneous fat loss and the metabolic improvements induced by CR. These results provide insights into the overall energy homeostasis during CR, and they suggest beige fat development as a common feature in conditions of negative energy balance.