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Bone marrow adipocytes alteration in an

A Crivaro1, J M Mucci1, C Bondar1

  • 1Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), Universidad Nacional de La Plata, CONICET, asociado CIC PBA, Facultad de Ciencias Exactas, Departamento de Ciencias Biológicas, Bv. 120 N1489 (1900), La Plata, Argentina.

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Summary

Gaucher disease (GD) adipocytes show altered lipid metabolism, with increased lipolysis and reduced lipid synthesis. These changes may contribute to bone complications in GD patients.

Keywords:
AdipocytesBoneGaucherLipid dropletsMSCs

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Genetics

Background:

  • Gaucher disease (GD) results from GBA1 gene variants, affecting glucocerebrosidase. Current treatments do not fully resolve bone complications.
  • Bone homeostasis relies on osteoblasts, osteocytes, and osteoclasts, with mature adipocytes influencing their function via secreted factors.
  • Mesenchymal stem cells (MSCs) differentiate into osteoblasts and adipocytes, impacting skeletal health.

Purpose of the Study:

  • To investigate potential alterations in Gaucher disease adipocytes (GD Ad) that may contribute to skeletal complications.
  • To evaluate lipid droplet (LD) metabolism and synthesis in GD Ad compared to control adipocytes.

Main Methods:

  • MSCs were cultured in adipogenic media to induce differentiation into adipocytes.
  • PPAR-γ expression was assessed to confirm adipocyte differentiation.
  • Lipid droplet accumulation, lipolysis (glycerol release), and synthesis enzymes (FASN, SCD1) were measured in GD Ad and control Ad.

Main Results:

  • GD Ad exhibited proper differentiation, indicated by nuclear PPAR-γ localization.
  • However, GD Ad accumulated fewer lipid droplets and showed increased glycerol release, suggesting enhanced lipolysis.
  • Transcription of lipid synthesis enzymes FASN and SCD1 was decreased in GD Ad, indicating impaired lipid synthesis.

Conclusions:

  • Gaucher disease adipocytes display altered lipid metabolism, characterized by increased lipolysis and reduced lipid synthesis, independent of the differentiation process.
  • These metabolic dysfunctions in GD Ad may play a significant role in the skeletal imbalance observed in Gaucher disease.