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

CRIVARO, ANDREA; BONDAR, CONSTANZA; MUCCI, J.; ORMAZABAL, M.; VAENA E; DELPINO, VICTORIA; ROZENFELD, P.

Simposio; 19th WORLD Symposium Lysosomal Disease Network; 2023

Gaucher disease (GD) is caused by mutations in GBA 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 continuously remodeling in order to maintain proper structure. It is composed by hematopoietic cells as machrophages and non hematopoietic cells as mesenchymal stem cells (MSCs). Depends on environment, MSCs could differentiate into osteoblasts and adipocytes, among other linages. It is known that an imbalance between these linages could lead to bone disease. Previously, we demonstrated a decrease function of GD osteoblast, thus the aim of this work is to evaluate possible alterations in GD adipocyte (GD Ad) that could contribute to bone problems. We proceeded to differentiate MSCs during 7 days with adipogenic media in order to determine differentiation markers as PPAR-γ. PPAR-γ was observed into the nucleus of GD Ad, indicating that are properly stimulated. However, these cells accumulate lesser lipid droplets than Control Ad. In order to study lipid droplet metabolism, we evaluate the lipolysis of these structures by the measurement of free glycerol in culture supernatant. Results indicated that GD Ad had an alteration in 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.