Interleukin-6 (IL6) produced in the context of exercise acts in the hypothalamus reducing obesity-associated inflammation and restoring the control of food intake and energy expenditure. In the hippocampus, some of the beneficial actions of IL6 are attributed to its neurogenesis-inducing properties. However, in the hypothalamus, the putative neurogenic actions of IL6 have never been explored, and its potential to balance energy intake can be an approach to prevent or attenuate obesity. Wild-type (WT) and IL6 knockout (KO) mice were employed to study the capacity of IL6 to induce neurogenesis. We used cell labeling with Bromodeoxyuridine (BrdU), immunofluorescence, and real-time PCR to determine the expression of markers of neurogenesis and neurotransmitters. We prepared hypothalamic neuroprogenitor cells from KO that were treated with IL6 in order to provide an ex vivo model to further characterizing the neurogenic actions of IL6 through differentiation assays. In addition, we analyzed single-cell RNA sequencing data and determined the expression of IL6 and IL6 receptor in specific cell types of the murine hypothalamus. IL6 expression in the hypothalamus is low and restricted to microglia and tanycytes, whereas IL6 receptor is expressed in microglia, ependymocytes, endothelial cells, and astrocytes. Exogenous IL6 reduces diet-induced obesity. In outbred mice, obesity-resistance is accompanied by increased expression of IL6 in the hypothalamus. IL6 induces neurogenesis-related gene expression in the hypothalamus and in neuroprogenitor cells, both from WT as well as from KO mice. IL6 induces neurogenesis-related gene expression in the hypothalamus of WT mice. In KO mice, the neurogenic actions of IL6 are preserved; however, the appearance of new fully differentiated proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons is either delayed or disturbed.

中文翻译：

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下丘脑中的白细胞介素 6 作用可防止肥胖并参与神经发生的调节

在运动背景下产生的白细胞介素 6 (IL6) 作用于下丘脑，减少与肥胖相关的炎症并恢复对食物摄入和能量消耗的控制。在海马体中，IL6 的一些有益作用归因于其诱导神经发生的特性。然而，在下丘脑中，IL6 的假定神经源性作用从未被探索过，其平衡能量摄入的潜力可以成为预防或减轻肥胖的一种方法。野生型 (WT) 和 IL6 敲除 (KO) 小鼠用于研究 IL6 诱导神经发生的能力。我们使用溴脱氧尿苷 (BrdU)、免疫荧光和实时 PCR 来确定神经发生和神经递质标志物的表达。我们从 KO 制备了用 IL6 处理的下丘脑神经祖细胞，以提供一种离体模型，以通过分化试验进一步表征 IL6 的神经源性作用。此外，我们分析了单细胞 RNA 测序数据，并确定了 IL6 和 IL6 受体在小鼠下丘脑特定细胞类型中的表达。下丘脑中的 IL6 表达低且仅限于小胶质细胞和单核细胞，而 IL6 受体在小胶质细胞、室管膜细胞、内皮细胞和星形胶质细胞中表达。外源性 IL6 可减少饮食引起的肥胖。在远交小鼠中，肥胖抵抗伴随着下丘脑中 IL6 的表达增加。IL6 在来自 WT 和 KO 小鼠的下丘脑和神经祖细胞中诱导神经发生相关基因表达。IL6 在 WT 小鼠的下丘脑中诱导神经发生相关基因表达。在 KO 小鼠中，IL6 的神经源性作用得以保留；然而，新的完全分化的阿片黑皮质素原 (POMC) 和神经肽 Y (NPY) 神经元的出现要么延迟要么受到干扰。