Macrophage depletion disrupts immune balance and energy homeostasis.
Macrophage depletion disrupts immune balance and energy homeostasis.
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DOI：
10.1371/journal.pone.0099575
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shao J
中科院分区：
文献类型：
--
作者：
Lee B;Qiao L;Kinney B;Feng GS;Shao J
在包括白色脂肪组织和骨骼肌的组织中增加的巨噬细胞浸润已经被认为是损害肥胖症中的胰岛素敏感性的促炎因子。然而，在非肥胖生理条件下，组织巨噬细胞与能量代谢之间的关系尚不清楚。为了研究巨噬细胞在能量稳态中的稳态作用，我们通过白喉毒素（DT）受体的条件性表达和DT诱导的细胞凋亡来消耗成年小鼠的组织巨噬细胞。由于减少能量摄入，巨噬细胞耗竭显著降低了体脂量。这些表型在巨噬细胞恢复后逆转。作为一种潜在的机制，在不存在巨噬细胞的情况下，中性粒细胞（NE）浸润诱导了严重的下丘脑和全身炎症。此外，巨噬细胞耗竭显着增加循环粒细胞集落刺激因子（G-CSF），这是必不可少的NE生产和组织浸润。我们的体外研究进一步揭示巨噬细胞直接抑制G-CSF基因表达。因此，我们的研究表明，巨噬细胞可能在生理条件下整合免疫平衡和能量稳态中发挥关键作用。
Increased macrophage infiltration in tissues including white adipose tissue and skeletal muscle has been recognized as a pro-inflammatory factor that impairs insulin sensitivity in obesity. However, the relationship between tissue macrophages and energy metabolism under non-obese physiological conditions is not clear. To study a homeostatic role of macrophages in energy homeostasis, we depleted tissue macrophages in adult mice through conditional expression of diphtheria toxin (DT) receptor and DT-induced apoptosis. Macrophage depletion robustly reduced body fat mass due to reduced energy intake. These phenotypes were reversed after macrophage recovery. As a potential mechanism, severe hypothalamic and systemic inflammation was induced by neutrophil (NE) infiltration in the absence of macrophages. In addition, macrophage depletion dramatically increased circulating granulocyte colony-stimulating factor (G-CSF) which is indispensable for NE production and tissue infiltration. Our in vitro study further revealed that macrophages directly suppress G-CSF gene expression. Therefore, our study indicates that macrophages may play a critical role in integrating immune balance and energy homeostasis under physiological conditions.
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