The antiadipogenic effect of macrophage-conditioned medium depends on EPK1/2 activation
The antiadipogenic effect of macrophage-conditioned medium depends on EPK1/2 activation
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DOI：
10.1016/j.metabol.2007.11.005
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发表时间：
2008-04-01
影响因子：
9.8
通讯作者：
Sorisky, Alexander
中科院分区：
文献类型：
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作者：
Constant, Vanessa A.;Gagnon, AnneMarie;Sorisky, Alexander
肥胖的动脉粥样硬化前状态与脂肪细胞肥大有关，脂肪细胞肥大可能是由于脂肪生成不足引起的。巨噬细胞由于肥胖而渗入脂肪组织，并可能释放抑制脂肪生成的因子。巨噬细胞条件培养液在培养中抑制人和3T3-L1脂肪细胞的分化，但其潜在的分子机制尚未明确。将3T3-L1细胞在8天的分化期内暴露于THP-1顶体噬菌体(THP-1-MacCM)条件培养液中，可抑制脂肪生成。三酰甘油(TG)蓄积和过氧化体增殖物激活受体T和脂肪酸合成酶蛋白水平的诱导分别被抑制59%(n=4，P<0.01)、29%(n=4，P<0.01)和47%(n=4，P<0.01)。在分化前2天加入THP-1-MacCM则没有作用，表明必须及早暴露其靶点以抑制3T3-L1脂肪生成。细胞计数显示克隆扩增较标准分化减少44%(n=3，P<；.01)。在3T3-L1前脂肪细胞中加入THP-1-MacCM可使ERK1/2磷酸化增加6.5倍(n=3，P<0.01)。PD98059(ERK1/2途径的抑制剂)减弱了THP-1-MacCM对甘油三酯积累的负面影响，其抑制程度为25%比69%(n=3，P<；.001)，而不改变脂肪酸合成酶或过氧化体增殖物激活受体γ的水平。我们的数据表明ERK1/2是THP-1-MacCM抑制3T3-L1成脂过程中TG积聚的重要信号介质。(C)2008 Elsevier Inc.保留所有权利。
The proatherogenic state of obesity is associated with hypertrophied adipocytes that may arise because of deficient adipogenesis. Macrophages infiltrate adipose tissue as a function of obesity and may release factors that attenuate adipogenesis. Macrophage-conditioned medium inhibits human and 3T3-L1 adipocyte differentiation in culture, but underlying molecular mechanisms have yet to be defined. Exposure of 3T3-L1 cells throughout the 8-day period of differentiation to medium conditioned by THP-1 inacrophages (THP-1-MacCM) blocked adipogenesis. Triacylglycerol (TG) accumulation and induction of peroxisome proliferator-activated receptor T and fatty acid synthase protein levels were inhibited by 59% (n = 4, P < .001) 29% (n = 4, P < .01), and 47% (n = 4, P < .01), respectively. THP-1-MacCM had no effect when added after the first 2 days of differentiation, indicating that early exposure of its targets must be needed to inhibit 3T3-L1 adipogenesis. Cell enumeration revealed a 44% decrease in clonal expansion compared with standard differentiation (n = 3, P < .01). Addition of THP-1-MacCM to 3T3-L1 preadipocytes increased ERK1/2 phosphorylation by 6.5-fold (n = 3, P < .01). PD98059 (an inhibitor of the ERK1/2 pathway) impaired the negative effect of THP-1-MacCM on TG accumulation, indicated by an inhibition of 25% vs 69% (n = 3, P < .001), without altering fatty acid synthase or peroxisome proliferator-activated receptor gamma levels. Our data implicate ERK1/2 as an important signaling mediator for the inhibitory effect of THP-1-MacCM on TG accumulation during 3T3-L1 adipogenesis. (c) 2008 Elsevier Inc. All rights reserved.