Favoring the resolution of adipose tissue fibrosis to improve obesity and type 2 diabetes – ResOB

Obesity is a complex disease, altering quality of life and life expectancy, for which innovative therapeutics approaches are urgently needed. Our team pioneered the description of excess deposition of extracellular matrix (ECM) resembling fibrosis in WAT depots of patients with obesity. We then contributed to establish WAT fibrosis as a critical determinant of WAT dysfunctions and clinical alterations, such as type 2 diabetes, as well as impaired weight loss (WL).
Our proposal ResOB aims to identify strategies stimulating WAT fibrosis clearance that could be used as an adjunct therapy during WL intervention to maximise outcomes. While much of the current scientific effort in WAT fibrosis field is focused on pathways that regulate increased collagen production, here we will assess whether stimulating collagen degradation improve WAT fibrosis and the glucose control in the context of WL. In addition, we propose, for the first time, to use mass spectrometry for the quantitative and qualitative characterization of WAT ECM proteins (matrisome) in order to identify matrisome alterations associated with WAT fibrosis remodeling. Together, ResOB will evaluate the contribution of collagenolysis in the WAT fibrosis and will identify other elements of the ECM as potential therapeutic targets.