Gagnon Annemarie, Yarmo Michelle N, Landry Anne, Sorisky Alexander
Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, General Campus C-4421, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada.
Lipids. 2012 Sep;47(9):873-80. doi: 10.1007/s11745-012-3696-8. Epub 2012 Jul 12.
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.
肥胖个体的脂肪组织具有纤维化增加和巨噬细胞浸润的特征。脂肪生成过程中发生的细胞外基质（ECM）广泛重塑可受巨噬细胞影响，但尚不清楚巨噬细胞分泌的因子在非脂肪生成与脂肪生成条件下如何改变前脂肪细胞ECM蛋白表达。将汇合的人腹部皮下前脂肪细胞在有或无脂肪生成诱导剂的情况下，于对照培养基、经THP-1单核细胞处理的培养基（THP-1-MonCM）或经THP-1巨噬细胞处理的培养基（THP-1-MacCM）中培养14天。在THP-1-MacCM的非脂肪生成条件下，I/III型胶原蛋白和纤连蛋白蛋白水平分别升高了40%和70%（p<0.05，n = 3；与对照非脂肪生成培养基相比）。当在THP-1-MacCM中将前脂肪细胞暴露于脂肪生成诱导剂时，与非脂肪生成的THP-1-MacCM条件相比，I/III型胶原蛋白水平增加了50%，但纤连蛋白水平下降了48%。I/III型胶原蛋白水平的升高与对照培养基中诱导分化时I/III型胶原蛋白51%的降低形成对比，而纤连蛋白的降低更为适度，但在THP-1-MacCM（48%）和对照培养基（92%）中是一致的。使用经脂多糖处理的人单核细胞衍生巨噬细胞处理的培养基（MD-MacCM）对纤连蛋白水平产生了类似的影响。我们的数据表明，巨噬细胞衍生的因子在非脂肪生成和脂肪生成条件下调节前脂肪细胞中I/III型胶原蛋白和纤连蛋白的水平。需要进一步研究以确定这些ECM蛋白的这些变化是否有助于MacCM的抗脂肪生成作用。
