Adipocyte-fibroblast Bidirectional Crosstalk Promotes Features of Fibrosis

Asthma remains a global disease with rising incidence. It is associated with multiple co-morbidities, where obesity is the most coupled co-morbidity and an important risk factor to severe asthma development. Recently, adipocytes were found to be present in the airway walls, positively correlating with their body mass index (BMI). However, their role in the airway remains unknown. This raises the question about their contribution to asthma airway remodeling, a major pathological feature constituting structural, cellular and extracellular matrix changes in the airways, including fibrosis, a highly progressive form of the disease. To our knowledge, this is the first study that aims to evaluate the influence of obesity on asthma remodeling via adipocyte-fibroblast bidirectional crosstalk. Using an in vitro co-culture model of fibroblasts (normal and asthmatic) and adipocytes (lean and obese), our preliminary data displayed a significant increase in the fibrogenic marker (α-SMA) in normal- fibroblasts co-cultured with lean- and obese- adipocytes; but not in the asthmatic counterpart. On the other hand, a notable increase in α-SMA expression was detected in adipocytes from obese subjects upon co-culturing with asthma- fibroblasts. This was accompanied with a significant reduction in the expression of adipogenic markers (PPARγ, leptin, and adiponectin), thus proposing the loss of their adipogenicity which may influence the pathogenesis of fibrosis. Taken together, this study will provide novel insights into the role of adiposity in the development of airway remodeling, particularly fibrosis. Moreover, it will advance our understanding in developing novel therapeutic strategies for obese asthmatic patients.