Obesity modifies bone marrow microenvironment and directs bone marrow mesenchymal cells to adipogenesis

• Published in: Obesity (Silver Spring, Md.) Md.), 2016-12, Vol.24 (12), p.2522-2532
• Main Authors: Silva, Simone Vargas, Renovato‐Martins, Mariana, Ribeiro‐Pereira, Cristiane, Citelli, Marta, Barja‐Fidalgo, Christina
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipogenesis - physiology; Animals; Bone Marrow; Bone Marrow Cells - physiology; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Differentiation; Cell Proliferation; Collagen; Diet, High-Fat; Inflammation; Laboratory animals; Male; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred C57BL; Obesity; Obesity - etiology; Obesity - physiopathology; PPAR gamma - metabolism; Stem cells; Studies; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21660

Objective To investigate the role of obesity on the bone marrow microenvironment and evaluate its possible impact on the adipogenic potential of mesenchymal stem cells (MSC). Methods C57BL/6 male mice were fed with a high‐fat diet (HFD) for 10 weeks. Femurs and tibiae were collected, and bone marrow mesenchymal stem cells (BM‐MSC) were isolated and analyzed for proliferative potential, immunophenotype, and expression of adipogenesis markers. Their capacity to produce extracellular matrix proteins and proinflammatory cytokines in vitro was also evaluated. Results HFD mice presented a significant increase in bone marrow cellularity and higher tumor necrosis factor‐α production in vitro. BM‐MSC from HFD mice had higher proliferative capacity, produced more extracellular matrix proteins associated with adipogenesis, collagen I, and collagen IV, and showed increased constitutive expression of adipogenic markers, peroxisome proliferator‐activated receptor‐γ, and CCAAT/enhanced binding protein family‐α, without changes in preadipocyte factor‐1 expression. Incubation with adipocyte‐differentiation medium induced further increase in CCAAT/enhanced binding protein family‐α and augmented adiponectin expression in obese BM‐MSC. These alterations did not result in increased adipogenic differentiation within the bone marrow. Moreover, BM‐HSC from HFD mice, co‐cultivated with BM‐MSCs from lean mice, exerted paracrine effects on these cells, inducing augment of peroxisome proliferator‐activated receptor‐γ. Conclusions The data suggest that obesity promotes an inflammatory microenvironment in bone marrow that commits BM‐MSC to adipogenesis.