Macrophage-secreted factors impair human adipogenesis: Involvement of proinflammatory state in preadipocytes
Macrophage-secreted factors impair human adipogenesis: Involvement of proinflammatory state in preadipocytes
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DOI：
10.1210/en.2006-0687
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发表时间：
2007-02-01
期刊：
影响因子：
4.8
通讯作者：
Clement, Karine
中科院分区：
文献类型：
--
作者：
Lacasa, Daniele;Taleb, Soraya;Clement, Karine
肥胖被认为是一种慢性低度炎症状态。白色脂肪组织产生多种与炎症相关的蛋白质，这些蛋白质的表达在肥胖受试者中增加。非脂肪细胞部分包括浸润的巨噬细胞，是脂肪组织内炎症相关分子的决定性来源。我们的工作假设是巨噬细胞浸润通过对脂肪细胞分化的旁分泌作用影响脂肪扩张。然后在从血单核细胞分化的巨噬细胞获得的条件培养基的存在下分化人原代前脂肪细胞。通过巨噬细胞条件培养基处理的前脂肪细胞显示出脂肪生成的显着减少，通过细胞脂质积累的减少以及脂肪生成和脂肪生成标记物的基因表达的减少来评估。除了这种作用之外，脂多糖对巨噬细胞的激活还刺激核因子κB信号传导，增加基因表达和促炎细胞因子和趋化因子的释放，并诱导前脂肪细胞增殖。这种现象与细胞周期蛋白 D1 基因表达增加和富含纤连蛋白基质的维持有关。抗 TNF α 中和抗体抑制前脂肪细胞的炎症状态，将 TNF α 定位为前脂肪细胞炎症的重要介质。引人注目的是，从人类脂肪组织中分离出的巨噬细胞产生的条件培养基与活化的巨噬细胞发挥了相当的作用，即减少了脂肪生成并增加了前脂肪细胞的炎症状态。这些数据表明巨噬细胞分泌的因子抑制成熟脂肪细胞的形成，表明其可能在限制人类脂肪组织扩张方面发挥作用。
Obesity is considered a chronic low-grade inflammatory state. The white adipose tissue produces a variety of inflammation-related proteins whose expression is increased in obese subjects. The nonadipose cell fraction, which includes infiltrated macrophages, is a determinant source of inflammation-related molecules within the adipose tissue. Our working hypothesis is that macrophage infiltration affects fat expansion through a paracrine action on adipocyte differentiation. Human primary preadipocytes were then differentiated in the presence of conditioned media obtained from macrophages differentiated from blood monocytes. Preadipocytes treated by macrophage-conditioned medium displayed marked reduction of adipogenesis as assessed by decreased cellular lipid accumulation and reduced gene expression of adipogenic and lipogenic markers. In addition to this effect, the activation of macrophages by lipopolysaccharides stimulated nuclear factor kappa B signaling, increased gene expression and release of proinflammatory cytokines and chemokines, and induced preadipocyte proliferation. This phenomenon was associated with increased cyclin D1 gene expression and maintenance of the fibronectin-rich matrix. Anti-TNF alpha neutralizing antibody inhibits the inflammatory state of preadipocytes positioning TNF alpha as an important mediator of inflammation in preadipocytes. Strikingly, conditioned media produced by macrophages isolated from human adipose tissue exerted comparable effects with activated macrophages, i.e. decreased adipogenesis and increased inflammatory state in the preadipocytes. These data show that macrophage-secreted factors inhibit the formation of mature adipocytes, suggesting possible role in limiting adipose tissue expansion in humans.