Macrophages Alter the Differentiation-Dependent Decreases in Fibronectin and Collagen I/III Protein Levels in Human Preadipocytes
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Adipose tissue of obese individuals is characterized by increased fibrosis and macrophage infiltration. Extensive remodeling of the extracellular matrix (ECM) that occurs during adipogenesis can be influenced by macrophages, but it remains unclear how macrophage-secreted factors alter preadipocyte ECM protein expression under non-adipogenic versus adipogenic conditions. Confluent human subcutaneous abdominal preadipocytes were cultured for 14 days, with or without adipogenic inducers, in either control medium, medium conditioned by THP-1 monocytes (THP-1-MonCM), or medium conditioned by THP-1 macrophages (THP-1-MacCM). Under non-adipogenic conditions in THP-1-MacCM, collagen I/III and fibronectin protein levels rose by 40 and 70 %, respectively (p < 0.05, n = 3; compared to control non-adipogenic medium). When preadipocytes were exposed to adipogenic inducers in THP-1-MacCM, collagen I/III levels increased by 50 %, but those of fibronectin fell by 48 %, both compared to non-adipogenic THP-1-MacCM conditions. The rise in collagen I/III levels contrasts with the 51 % decrease in collagen I/III that occurs with induction of differentiation in control medium, whereas, the decrease in fibronectin is more modest, but consistent in THP-1-MacCM (48 %) and control medium (92 %). A similar effect on fibronectin levels occurred using medium conditioned by LPS-treated human monocyte-derived macrophages (MD-MacCM). Our data indicate macrophage-derived factors regulate levels of collagen I/III and fibronectin in preadipocytes under non-adipogenic and adipogenic conditions. Further studies are needed to determine if these changes in these ECM proteins contribute to the anti-adipogenic action of MacCM.
KeywordsPreadipocyte Adipogenesis Fibronectin Collagen Extracellular matrix Macrophage
Body mass index
Extracellular signal-regulated kinase 1/2
Fatty acid binding protein 4
Integrated optical density
Peroxisome proliferator-activated receptor γ
Tissue inhibitor of matrix metalloproteinase
Tumor necrosis factor α
This work was supported by a grant to AS from the Heart and Stroke Foundation of Canada (Ontario) NA 6634. We thank Fiona Frappier and Dr. J B Angel (OHRI) for assistance with production of MD-MacCM, and patients and surgeons of The Ottawa Hospital for their participation in acquiring adipose tissue samples.
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