Background

Obesity may impact the bone marrow microenvironment, disrupting leukocyte production and increased bone marrow adiposity. We have investigated the impact of obesity on the migratory and adipogenic potential of bone marrow mesenchymal stem cells.

Methods

Bone marrow mesenchymal stem cells (BM-MSC) were isolated from femurs and tibiae from C57BL/6 male mice, fed with a high fat (45%) diet for 10 weeks. Cells were analyzed for proliferative potential, expression of adipogenic markers, capacity to produce extracellular matrix proteins and proinflammatory cytokines in vitro. The frequency of MSC in bone marrow, blood and visceral adipose tissue (VAT) invivo and its migratory potential in vitro was also evaluated.

Results

Diet-induced obesity increased the proliferative capacity of BM-MSC and induced higher production of TNF-α and of adipogenesis-associated matrix proteins, collagen I and collagen IV. BM-MSC from obese mice presented increased constitutive expression of adipogenic markers, peroxisome proliferator-activated receptor-y (PPAR-y) and CCAAT/enhanced binding protein family-α (CEBP-α), without changes in preadipocyte factor-1 expression (PREF-1). Incubation of obese BM-MSC in adipocyte-differentiation medium induced further increase in CEBP-α and adiponectin expressions, without any alterations in the adipogenic differentiation or in the content of MSC within the BM niche. However, obesity increased BM-MSC frequency in the blood and VAT. The BM-MSC from obese mice displayed an upregulation of the CXCR4 chemokine receptor, showing enhanced spontaneous migration, but a mild chemotactic activity towards SDF-1α, in vitro.

Conclusions

The data indicated that obesity promotes an inflammatory microenvironment in bone marrow that commits BM-MSC to adipogenesis, increases their migratory potential, inducingBM-MSC accumulation in the VAT.