Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Horm Metab Res. 2010 Nov;42(12):831-6. doi: 10.1055/s-0030-1263124. Epub 2010 Aug 27.
Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is not well understood. Our objective was to determine if anti-adipogenic signaling pathways in human preadipocytes are activated by macrophage-conditioned medium (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with adipogenic inducers in either standard medium or medium conditioned by human THP-1 macrophages. THP-1-MacCM increased inhibitor of κB kinase β (IKKβ) phosphorylation, inhibitor of NF-κB α (IκBα) degradation, and NF-κB activity in human preadipocytes in a time-dependent manner. Concomitant treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective inhibitor of IKKβ, prevented the inhibitory effect of THP-1-MacCM on lipid accumulation and expression of adipogenic markers. Our data indicate that activation of the preadipocyte IKKβ/NF-κB pathway is required for the anti-adipogenic effect of THP-1-MacCM on human adipogenesis.
巨噬细胞分泌的因子可抑制脂肪生成，但其中的作用机制尚未完全阐明。我们的目的是确定人源前体脂肪细胞中的抗脂肪生成信号通路是否被巨噬细胞条件培养基（MacCM）激活。用诱导剂在标准培养基或人 THP-1 巨噬细胞条件培养基中处理人腹部皮下基质前体脂肪细胞。THP-1-MacCM 以时间依赖性方式增加人前体脂肪细胞中 IκB 激酶β（IKKβ）磷酸化、NF-κBα（IκBα）降解和 NF-κB 活性。用选择性 IKKβ抑制剂 sc-514 同时处理人腹部皮下前体脂肪细胞可防止 THP-1-MacCM 对脂质积累和脂肪生成标志物表达的抑制作用。我们的数据表明，THP-1-MacCM 对人脂肪生成的抗脂肪生成作用需要前体脂肪细胞 IKKβ/NF-κB 途径的激活。
