Regulation of adipose tissue inflammation by interleukin 6
Regulation of adipose tissue inflammation by interleukin 6
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DOI：
10.1073/pnas.1920004117
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发表时间：
2020-02-11
影响因子：
11.1
通讯作者：
Davis, Roger J.
中科院分区：
文献类型：
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作者：
Han, Myoung Sook;White, Alexis;Davis, Roger J.
肥胖与低度炎症的慢性状态、免疫细胞的进行性组织渗透和炎性细胞因子的表达增加有关。白介素6(IL6)调节代谢的多个方面，包括葡萄糖代谢、脂肪分解、氧化代谢和能量消耗。IL6由许多组织分泌，但单个细胞类型的作用尚不清楚。我们使用条件表达IL6基因的小鼠模型测试了特定细胞的作用。我们发现来源于脂肪细胞的IL6增加，而来源于髓系细胞和肌肉的IL6抑制了脂肪组织的巨噬细胞的浸润。这些相反的作用与IL6信号从经典模式(髓样细胞)转换到非规范的反式信号模式(脂肪细胞和肌肉)有关，并伴随着ADAM10/17金属蛋白酶的表达增加，该酶促进了可溶性IL6受体a的反式信号转导。
Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor a. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.