Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Cell Rep. 2019 Mar 12;26(11):3011-3026.e5. doi: 10.1016/j.celrep.2019.02.044.
Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6.
慢性低度炎症和细胞因子 IL-6 血清水平升高伴随着肥胖。对于脑产生的 IL-6，其控制能量平衡的机制及其在肥胖中的作用尚不清楚。在这里，我们表明，脑产生的 IL-6 在肥胖小鼠和大鼠中以神经解剖学和性别特异性的方式减少。减少的 IL-6 mRNA 定位于外侧臂旁核 (lPBN) 星形胶质细胞、小胶质细胞和神经元，包括室旁下丘脑支配的 lPBN 神经元。将 IL-6 微注射到 lPBN 中，通过增加甲状腺和去甲肾上腺素能神经对 BAT 的输出，减少雄性瘦鼠和肥胖鼠的食物摄入并增加棕色脂肪组织 (BAT) 的产热。臂旁 IL-6 与瘦素相互作用以减少进食。lPBN IL-6 的 siRNA 介导减少导致体重增加和肥胖增加、BAT 产热减少和食物摄入增加。周围寒冷暴露部分正常化肥胖诱导的 lPBN IL-6 抑制。这些结果表明，lPBN 产生的 IL-6 调节摄食和代谢，并确定与 lPBN IL-6 相互作用的（病理）生理环境。
