Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, USA.
Cell Stem Cell. 2020 Jun 4;26(6):880-895.e6. doi: 10.1016/j.stem.2020.03.013. Epub 2020 Apr 16.
Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation after injury and promote subsequent repair. We find through histological, ultrastructural, lipidomic, and genetic experiments in mice that adipocytes adjacent to skin injury initiate lipid release necessary for macrophage inflammation. Tamoxifen-inducible genetic lineage tracing of mature adipocytes and single-cell RNA sequencing revealed that dermal adipocytes alter their fate and generate ECM-producing myofibroblasts within wounds. Thus, adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.
成熟的脂肪细胞储存脂肪酸，是组织基质的常见组成部分。脂肪细胞在调节骨髓、皮肤、肌肉和乳腺生物学方面的功能正在逐渐显现，但脂肪细胞衍生的脂质在组织稳态和修复中的作用还知之甚少。在这里，我们确定了脂肪细胞脂解在调节皮肤损伤后炎症和修复中的重要作用。遗传小鼠研究表明，真皮脂肪细胞是损伤后引发炎症和促进随后修复所必需的。我们通过小鼠的组织学、超微结构、脂质组学和遗传实验发现，紧邻皮肤损伤的脂肪细胞启动了巨噬细胞炎症所需的脂质释放。用他莫昔芬诱导的成熟脂肪细胞遗传谱系追踪和单细胞 RNA 测序显示，真皮脂肪细胞改变其命运，并在伤口中产生产生细胞外基质的肌成纤维细胞。因此，脂肪细胞调节修复的多个方面，可能对与衰老和糖尿病相关的炎症性疾病和伤口愈合不良具有治疗作用。
