Jessica L Wager, Larissa G Baker, Taylor B Scheidl, Sophie Z Yonan, Pina Colarusso, Daniel Young, Antoine Dufour, Jennifer A Thompson
{"title":"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。","authors":"Jessica L Wager, Larissa G Baker, Taylor B Scheidl, Sophie Z Yonan, Pina Colarusso, Daniel Young, Antoine Dufour, Jennifer A Thompson","doi":"10.1152/ajpcell.00024.2025","DOIUrl":null,"url":null,"abstract":"<p><p>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 (H<sub>2</sub>O<sub>2</sub>) 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.<b>NEW & NOTEWORTHY</b> 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.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"328 6","pages":"C1730-C1742"},"PeriodicalIF":5.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interleukin-6 from the adipose secretome potentiates differentiation of adipose progenitors through the activation of redox signaling.\",\"authors\":\"Jessica L Wager, Larissa G Baker, Taylor B Scheidl, Sophie Z Yonan, Pina Colarusso, Daniel Young, Antoine Dufour, Jennifer A Thompson\",\"doi\":\"10.1152/ajpcell.00024.2025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (H<sub>2</sub>O<sub>2</sub>) 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.<b>NEW & NOTEWORTHY</b> 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.</p>\",\"PeriodicalId\":7585,\"journal\":{\"name\":\"American journal of physiology. 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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.
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.