van den Berg Susan M, van Dam Andrea D, Kusters Pascal J H, Beckers Linda, den Toom Myrthe, van der Velden Saskia, Van den Bossche Jan, van Die Irma, Boon Mariëtte R, Rensen Patrick C N, Lutgens Esther, de Winther Menno P J
Department of Medical BiochemistryExperimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of MedicineDivision Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
J Mol Endocrinol. 2017 Oct;59(3):245-255. doi: 10.1530/JME-17-0112. Epub 2017 Jul 10.
Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from or and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes.
棕色脂肪组织（BAT）的激活和白色脂肪组织（WAT）的米色化可增加能量消耗，并有可能减少肥胖及相关疾病。免疫系统是介导棕色和米色脂肪细胞激活的一个潜在靶点。2型和抗炎免疫细胞有助于瘦的白色脂肪组织内的代谢稳态，嗜酸性粒细胞和白细胞介素（IL）-4诱导的抗炎巨噬细胞发挥着重要作用。我们测定了C57Bl/6小鼠在高脂饮食（HFD）喂养1天、3天或1周后附睾白色脂肪组织（EpAT）、皮下白色脂肪组织（ScAT）和棕色脂肪组织中的嗜酸性粒细胞数量。高脂饮食1天导致附睾白色脂肪组织和棕色脂肪组织中的嗜酸性粒细胞数量迅速下降，3天后皮下白色脂肪组织中的嗜酸性粒细胞数量也下降。为了试图恢复高脂饮食引起的脂肪组织嗜酸性粒细胞数量下降，我们用来自或的蠕虫抗原处理高脂饮食喂养1周的小鼠，并评估蠕虫抗原众所周知的保护性代谢作用是否涉及棕色脂肪组织的激活或米色化。事实上，两种蠕虫的抗原都在附睾白色脂肪组织中诱导了大量嗜酸性粒细胞，但未能诱导米色化。在皮下白色脂肪组织中，抗原诱导了轻度嗜酸性粒细胞增多，同时伴有稍多的米色化。在棕色脂肪组织中未观察到影响。为了直接研究对棕色脂肪细胞的2型反应，用IL-4刺激T37i细胞。这增加了表达，并强烈诱导嗜酸性粒细胞趋化因子CCL11的产生（增加26倍），表明棕色脂肪细胞本身可以吸引嗜酸性粒细胞。我们的研究结果表明，蠕虫抗原诱导的嗜酸性粒细胞增多未能诱导白色脂肪细胞的深度米色化。
