Anales RANF

P.104 ROLE OF ADENOSINE IN ADIPOSE TISSUE FIBROSIS B. Niemann, S. Haufs-Brusberg and A. Pfeifer University of Bonn, Bonn, Germany Two types of adipose tissue can be distinguished: white and brown adipose tissue. White adipose tissue (WAT) plays an important role as energy storage. Brown adipose tissue (BAT) is not primarily used for energy storage, but is characterized by energy dissipation and thermogenic function. BAT generates heat via the numerous mitochondria that contain the uncoupling protein 1 (UCP1) by uncoupling ATP synthesis (non-shivering-thermogenesis). It has been shown that obesity is associated with fibrosis in WAT. The resulting deposition of collagen fibers causes insulin resistance [1]. Interestingly, during obesity, BAT adapts a white fat-like phenotype. This process is also known as whitening, and fibrosis in the tissue can be observed [2]. However, the mechanisms underlying fibrosis in BAT are not well understood. We established a method to isolate primary fibroblasts of different fat depots. The preliminary data show an increased number of fibroblasts in BAT after feeding mice a high fat diet (60% kcal from fat) compared to a control diet (13% kcal from fat). Moreover, the adenosine receptor A2B (ADORA2b) is highly expressed in BAT- derived fibroblasts compared to the other adenosine-receptor-subtypes and its expression is also increased after feeding mice a high fat diet. Therefore, we focused on the role of the ADORA2b in BAT fibrosis, using ADORA2b deficient (ADORA2b-/-) mice. The ADORA2b-/- mice have a higher expression of profibrotic genes, such as collagens and TGF β in BAT compared to ADORA2b+/+ mice. Furthermore, the Sirius Red Stainings of BAT and WAT of ADORA2b-/- mice show a higher amount of collagen fibers than in the wild-type mice. Our data indicate that ADORA2b plays a role in fibrotic processes in adipose tissue. References: 1) Marcelin et al. A PDGFRa-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis. Cell Metabolism 2017.25, 1–13 2) Halberg et al. Hypoxia-Inducible Factor 1 α Induces Fibrosis and Insulin Resistance in White Adipose Tissue. Mol Cell Biol. 2009. 29(16): 4467–4483