Interleukin-6 actions in the hypothalamus protects against obesity and is involved in the regulation of neurogenesis.
Interleukin-6 actions in the hypothalamus protects against obesity and is involved in the regulation of neurogenesis.
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DOI：
10.1186/s12974-021-02242-8
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发表时间：
2021-08-31
影响因子：
9.3
通讯作者：
Araujo EP
中科院分区：
文献类型：
--
作者：
Bobbo VC;Engel DF;Jara CP;Mendes NF;Haddad-Tovolli R;Prado TP;Sidarta-Oliveira D;Morari J;Velloso LA;Araujo EP
在运动的背景下产生的白介素6(IL6)作用于下丘脑，减少肥胖相关的炎症，恢复对食物摄入量和能量消耗的控制。在海马区，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可能的神经源性作用从未被探索过，它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。用野生型(WT)和白介素6基因敲除(KO)小鼠研究白介素6诱导神经发生的能力。我们用溴脱氧尿苷(BrdU)细胞标记、免疫荧光和实时定量聚合酶链式反应(Real-time PCR)来检测神经发生和神经递质的标志物的表达。我们从KO中分离出神经前体细胞，用IL6诱导其分化，为进一步研究IL6的神经分化作用提供了体外模型。此外，我们分析了单细胞RNA测序数据，并测定了IL6和IL6受体在特定细胞类型的小鼠下丘脑中的表达。IL6在下丘脑中的表达很低，仅限于小胶质细胞和松弛细胞，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可减少饮食诱导的肥胖。在近交系小鼠中，肥胖抵抗伴随着下丘脑IL6表达的增加。IL6诱导WT和KO小鼠的下丘脑和神经前体细胞中神经发生相关基因的表达。IL-6诱导WT小鼠下丘脑神经发生相关基因表达在KO小鼠中，IL6的神经发生作用被保留下来；但是，新的完全分化的前阿片黑素皮质素(POMC)和神经肽Y(NPY)神经元的出现被推迟或被干扰。网上版载有补充材料，可在10.1186/s12974-021-02242-8查阅。
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. The online version contains supplementary material available at 10.1186/s12974-021-02242-8.
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影响因子：
4.3
作者：
Goodman T;Hajihosseini MK
通讯作者：
Hajihosseini MK
影响因子：
3.4
作者：
Balasubramaniam, Balini;Carter, Debra A.;Dick, Andrew D.
通讯作者：
Dick, Andrew D.
影响因子：
2.9
作者：
Desai M;Li T;Ross MG
通讯作者：
Ross MG
影响因子：
3.2
作者：
Bless EP;Reddy T;Acharya KD;Beltz BS;Tetel MJ
通讯作者：
Tetel MJ
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG