Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease

CRIVARO, ANDREA; BONDAR, CONSTANZA; MUCCI, JUAN MARCOS; ORMAZABAL MAXIMILIANO; VAENA EMILIO; DELPINO MV; ROZENFELD, PAULA ADRIANA

Simposio; Lysosomal Disease Network-17th Annual WORLD Symposium; 2023

Gaucher disease (GD) is caused by mutations in GBA1 gene that encodes the lysosomal enzyme glucocerebrosidase. Up to now, specific treatment for GD cannot completely reverse bone problems. Bone is a dynamic tissue that is in continuous remodeling in order to maintain proper structure. It is composed by cells of different origins, such as osteoclasts, osteoblasts, osteocytes mesenchymal stem cells (MSCs). Depending on the microenvironment, MSCs could differentiate into osteoblasts or adipocytes, among other linages. It is known that an imbalance between these linages could lead to bone disease. Previously, we have demonstrated GD osteoblasts present a decreased function of bone matrix formation. The aim of this work is to evaluate possible alterations in GD adipocyte (GD Ad) that may contribute to bone problems. MSCs were differentiated with adipogenic media. Staining of PPAR-γ was detected in the nucleus of GD Ad, indicating adipogenesis process is stimulated. However, these cells accumulate lesser lipid droplets than Control Ad. In order to study lipid droplet (LDs) metabolism, we evaluated lipolysis of LDs. Our results indicated GD Ad had an exacerbation of this process, evidenced by an increase in glycerol release. We have also evaluated two enzymes involved in LDs synthesis: fatty acid synthase (FASN) and stearoyl-coenzyme A desaturase 1 (SCD1). The expression of these genes was decreased in GD Ad, suggesting a dysfunction in the synthesis of LDs. In conclusion, our results show an alteration in lipid droplet metabolism of GD Ad, independent of adipocyte differentiation process, which could contribute with the skeletal imbalance in GD.