A Macrophage-Collagen Fragment Axis Mediates Subcutaneous Adipose Tissue Remodeling

ABSTRACT: Efficient collagen degradation is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we aimed 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 diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, the collagen endocytosis engagement of SAT macrophages is dramatically reduced in obesity along with elevated levels of short collagen fragments. Finally, we show that such fragments provoke M2-macrophage proliferation and fibroinflammatory changes in vitro. Thus, our data delineate the importance of a macrophage-collagen axis in physiological SAT expansion. Further understanding of this process can define novel targets in obesity-related disorders.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Subcutaneous Adipose Tissue

SUBMITTER: Johannes Fuchs  

LAB HEAD: Carina Sihlbom

PROVIDER: PXD043721 | Pride | 2024-06-16

REPOSITORIES: Pride