IL-10信号重塑脂肪染色体结构以限制热生成和能量消耗
Prashant Rajbhandari1, Brandon J Thomas2, An-Chieh Feng2
1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|December 19, 2017
概括
通过去除抗炎细胞因特鲁金-10 (IL-10) 增加能量消耗,并对抗肥胖. 这表明IL-10是白色脂肪组织中热生成的关键限制剂.
科学领域:
- 代谢和内分泌学
- 免疫学
- 细胞生物学
背景情况:
- 热生成是生物体产生热量的过程,对于能量消耗和代谢健康至关重要.
- 虽然促进热生成的途径已知,但限制能源消耗的因素在很大程度上仍未确定.
- 炎症信号通路越来越多地被认为是调节脂肪组织功能.
研究的目的:
- 研究抗炎细胞因特鲁金-10 (IL-10) 在限制脂肪组织热生成和能量消耗方面的作用.
- 在代谢调节的背景下识别IL-10信号的细胞来源和点.
- 阐明IL-10影响脂肪细胞中热生成基因表达的分子机制.
主要方法:
- 在小鼠模型中切除IL-10以评估对胰岛素敏感性,肥胖和脂肪组织色的影响.
- 通过机理学研究确定IL-10来源 (骨髓细胞) 和目标细胞 (脂肪细胞).
- 在各种条件下 (分化,肥胖,衰老) 分析IL-10受体α (IL-10RA) 表达.
- 使用染色体可访问性 (ATAC-seq),ChIP-seq和RNA-seq来确定IL-10的转录调节机制.
主要成果:
- 消去IL-10显著改善了胰岛素敏感性,并防止了饮食引起的肥胖.
- 失去了IL-10诱导了白色脂肪组织的棕色化,这是热生成活性增加的标志.
- 骨髓细胞被确定为IL-10的来源,脂肪细胞作为主要点细胞.
- 发现IL-10受体α在成熟脂肪细胞中表达高,并且随着分化,肥胖和衰老而上调.
- 通过改变染色质可访问性和抑制脂肪细胞中的转录因子结合 (ATF,C/ EBPβ),IL-10被证明可以抑制发热基因转录.
结论:
- 介素-10 作为白色脂肪组织中热生成的关键抑制剂.
- 源自骨髓的IL-10信号,对脂肪细胞起作用,在限制能量消耗和促进肥胖方面发挥着重要作用.
- 了解IL-10的作用机制为热生成的调节和代谢障碍的潜在治疗点提供了新的见解.
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