Collagen-degrading macrophages in subcutaneous adipose tissue expansion

The overall aim of this project is to provide a new mechanism for the interindividual differences in the capacity for subcutaneous adipose tissue expansion that in turn prevents harmful lipid deposition in the visceral compartment.Efficient collagen degradation is important for physiological adipose tissue expansion during development and in adulthood.

Our preliminary data show that the collagen loss in expanding subcutaneous adipose tissue is linked to increased proliferation of M2-like macrophages that display high collagen endocytosis capacity ex vivo.

We hypothesize that macrophage-mediated degradation of collagen fragments plays an important role in the physiological expansion of subcutaneous adipose tissue, and that increased testosterone and reduced adiponectin levels in men, as well as in women with polycystic ovary syndrome, reduce the subcutaneous adipose tissue expandability through effects on collagen turnover.

Finally, we hypothesize that adipocyte-derived extracellular vesicles trigger macrophages to become more efficient collagen degraders and that caveolin-1 facilitates this process.To test these hypotheses, we will primarily use mouse models but also human adipose tissue. Our methodology includes e.g.

FACS- and histological analyses, and ex vivo analysis of adipose tissue-resident macrophages.A successful outcome of this project will pave the way for future discoveries in this area and may also reveal new therapeutic targets for obesity-associated diseases.