来自脂肪分泌组的白细胞介素-6通过激活氧化还原信号通路增强了脂肪祖细胞的分化。

IF 5 2区 生物学 Q2 CELL BIOLOGY
Jessica L Wager, Larissa G Baker, Taylor B Scheidl, Sophie Z Yonan, Pina Colarusso, Daniel Young, Antoine Dufour, Jennifer A Thompson
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引用次数: 0

摘要

在肥胖条件下,人们认为脂肪微环境产生的信号触发了脂肪祖细胞(APCs)的分化;然而,这个信号的身份和来源仍然未知。研究表明,氧化还原信号可以影响原代小鼠APCs的脂肪生成,这些APCs通过药物处理来控制活性氧(ROS)的水平。通过氧化还原循环剂产生的超氧化物([公式:见文本])和过氧化氢(H2O2)增加了APC的分化,而ROS清除剂和抗氧化剂则使分化变得迟钝。从体外培养的脂肪组织外植体的条件培养基中浓缩蛋白质,以捕获分泌因子。在脂肪蛋白分泌组存在的情况下,apc的分化增强,这种作用随着清除ROS而减弱,当从喂食高脂肪饮食的小鼠中收集分泌组时,这种作用被放大。蛋白质组学分析显示,高脂肪饮食动物的脂肪分泌组在参与免疫细胞反应的途径中富集,并且含有更高水平的细胞因子,包括白细胞介素6 (IL-6)。多重分析证实了较高的IL-6,这被预测为分泌组蛋白差异水平的中心调节因子。将apc暴露于IL-6中会增加脂肪形成,而用IL-6阻断抗体治疗apc会降低脂肪分泌组的成脂作用。总之,这些发现证实了氧化还原信号在脂肪形成调控中的作用,并确定IL-6是一种潜在的分泌因子,可能在致肥条件下通过ROS生成介导脂肪形成的激活。这项研究发现IL-6是一种脂肪分泌因子,在肥胖中增加,并增强apc的分化。氧化还原信号参与APC分化并介导IL-6的促脂肪作用。因此,IL-6可能是肥胖情况下APC分化的旁分泌调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleukin-6 from the adipose secretome potentiates differentiation of adipose progenitors through the activation of redox signaling.

Under obesogenic conditions, it is thought that a signal arising from the adipose microenvironment triggers differentiation of adipose progenitor cells (APCs); yet the identity and source of this signal remain unknown. Redox signaling was shown to influence adipogenesis in primary murine APCs treated with pharmacological agents to manipulate the levels of reactive oxygen species (ROS). Increased generation of superoxide ([Formula: see text]) and hydrogen peroxide (H2O2) via redox cyclers amplified APC differentiation, while differentiation was blunted with ROS scavengers and antioxidants. Protein was concentrated from conditioned media of adipose tissue explants cultured ex vivo to capture secreted factors. Differentiation was enhanced in APCs cultured in the presence of the adipose protein secretome, an effect that was diminished with scavenging of ROS and amplified when the secretome was collected from mice fed a high-fat diet. Proteomic analysis revealed that the adipose secretome from animals on a high-fat diet was enriched in pathways involved in immune cell responses and contained higher levels of cytokines, including interleukin 6 (IL-6). A multiplex assay confirmed higher IL-6, which was predicted as a central regulator of differential levels of secretome proteins. Exposure of APCs to IL-6 increased adipogenesis, while treatment of APCs with an IL-6 blocking antibody diminished the adipogenic effect of the adipose secretome. Together, these findings substantiate a role for redox signaling in the regulation of adipogenesis and identify IL-6 as a potential secreted factor that may mediate activation of adipogenesis via ROS generation under obesogenic conditions.NEW & NOTEWORTHY This study identified IL-6 as an adipose-secreted factor that is increased in obesity and potentiates differentiation of APCs. Redox signaling is involved in APC differentiation and mediates the proadipogenic effect of IL-6. Thus, IL-6 may be a paracrine regulator of APC differentiation in the setting of obesity.

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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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