Global matrisome changes in obese lung are linked to fibroblastic stroma and premature aging

Obesity is linked to an increased risk of various lung disorders, yet its role in disease progression remains poorly understood. We have utilized multiomics approaches together with functional assays to explore the effect of obesity on the lung. Obesity induced matrisome remodeling and structural alterations in the elastic fiber network, exhibiting solubility shifts that overlapped with those seen in the aging lung. In addition, protease inhibitor levels were reduced in lung tissue and bronchoalveolar lavage fluid, suggesting a more damage-prone environment. At the cellular level, fibroblastic stromal cells (FSCs) selectively accumulated lipids, adopted myofibroblast-like phenotypes, and exhibited transcriptional hallmarks of premature aging. Functional assays confirmed that lipid-enriched fibroblasts displayed enhanced contractility, implicating them in the altered mechanical compliance of the obese lung. Overall, obesity led to complex alterations in the lung that ultimately affect FSCs and suggest that overnutrition may act as a contributor to premature aging, thereby compromising lung heath.