A macrophage-collagen fragment axis in the regulation of adipose tissue functionality

Milica Vujičić; Isabella Broderick; Pegah Salmantabar; Charlene Perian; Jonas Nilsson; Wallem Carina  Sihlbom; Asterholm Ingrid Wernstedt

doi:10.1530/endoabs.99.S8.1

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Endocrine Abstracts (2024) 99 S8.1 | DOI: 10.1530/endoabs.99.S8.1

ECE2024 Symposia Novel pathological aspects of adipose tissue (3 abstracts)

A macrophage-collagen fragment axis in the regulation of adipose tissue functionality

Milica Vujičić , Isabella Broderick , Pegah Salmantabar , Charlène Perian , Jonas Nilsson , Carina Sihlbom Wallem & Ingrid Wernstedt Asterholm

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University of Gothenburg, Sweden

Efficient removal of fibrillar collagen is essential for adaptive expansion of subcutaneous adipose tissue (SAT); a process that protects against deleterious ectopic lipid deposition in the visceral compartment during weight gain. Fibrillar collagen degradation in adipose tissue is initiated by extracellular collagenases, and we recently found that SAT-resident M2-like macrophages remove the fragmented collagen via endocytosis and lysosomal degradation. Moreover, these macrophages’ engagement in collagen endocytosis is diminished in obesity/insulin resistance associated with elevated levels of collagen fragments that exert fibroinflammatory changes in fibroblasts. Accordingly, we propose that collagen sequences that normally are hidden within the triple-helical structure of fibrillar collagen act as endogenous danger signals. Our new data within this area indicate that our findings translate to the clinic. We have also observed sex differences; female M2-like macrophages are more engaged in collagen endocytosis than those of males. 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 mean to improve adipose tissue function in obesity, which in turn may reduce the risk for metabolic disorders.