脂肪组织
巨噬细胞
皮下脂肪
皮下脂肪组织
组织重塑
细胞生物学
脂肪组织巨噬细胞
化学
生物
内分泌学
白色脂肪组织
免疫学
生物化学
炎症
体外
作者
Milica Vujičić,Isabella Broderick,Pegah Salmantabar,Charlène Perian,Jonas Nilsson,Carina Sihlbom Wallem,Ingrid Wernstedt Asterholm
标识
DOI:10.1073/pnas.2313185121
摘要
Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages’ engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.
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