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 α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.

中文翻译：

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白细胞介素 6 对脂肪组织炎症的调节。

肥胖与慢性低度炎症和免疫细胞进行性组织浸润以及炎性细胞因子表达增加有关。已确定白细胞介素 6 (IL6) 调节代谢的多个方面，包括葡萄糖处理、脂肪分解、氧化代谢和能量消耗。IL6 由许多组织分泌，但个别细胞类型的作用尚不清楚。我们使用具有条件性 Il6 基因表达的小鼠模型测试了特定细胞的作用。我们发现来自脂肪细胞的 IL6 增加，而来自骨髓细胞和肌肉的 IL6 抑制，脂肪组织的巨噬细胞浸润。这些相反的作用与 IL6 信号从典型模式（骨髓细胞）到非典型反式信号模式（脂肪细胞和肌肉）的转换有关，ADAM10/17 金属蛋白酶的表达增加，促进可溶性 IL6 受体的反式信号α。总的来说，这些数据表明 IL6 的产生来源在代谢的生理调节中起着重要作用。