In vitro aging of 3T3-L1 mouse adipocytes leads to altered metabolism and response to inflammation
In vitro aging of 3T3-L1 mouse adipocytes leads to altered metabolism and response to inflammation
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DOI：
10.1007/s10522-009-9236-0
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发表时间：
2010-02-01
期刊：
影响因子：
4.5
通讯作者：
Zamboni, Mauro
中科院分区：
文献类型：
--
作者：
Zoico, Elena;Di Francesco, Vincenzo;Zamboni, Mauro
我们使用体外模型来评估细胞衰老和炎症对脂肪细胞基因表达和蛋白分泌谱的影响。根据标准条件培养3 T3-L1小鼠前脂肪细胞，并在基础状态和用LPS急性刺激后的不同时间点进行分析。CCAAT/增强子结合蛋白（C/EBP）α、过氧化物酶体增殖物激活受体（PPAR）γ和S100 A1的mRNA水平在脂肪细胞分化过程中达到最高，然后显著下降。GLUT 4和IRS-1基因的表达在分化过程中达到高峰，然后在衰老细胞中下降。脂联素的mRNA水平和分泌随着脂肪细胞的成熟迅速上升，然后下降。IL 6的mRNA水平及其分泌随着前脂肪细胞的成熟和衰老而增加; MCP-1也有类似的趋势。LPS在所有时间点降低C/EBP α和PPAR γ的mRNA水平，以及GLUT 4、IRS-1和脂联素的mRNA水平。LPS显著增加IL-6的mRNA水平及其分泌，对于MCP-1也观察到类似的趋势。这些数据表明，在体外老化的脂肪细胞表现出下降的前脂肪形成的信号，在参与葡萄糖代谢和细胞骨架的维护和脂联素的基因。这些变化被炎性细胞因子的增加所掩盖;炎症似乎模拟并放大了细胞衰老对脂肪细胞的影响。
We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene expression and protein secretion profiles of adipocytes. 3T3-L1 mouse preadipocytes were cultured according to standard conditions and analyzed at different time points both at the basal state and after an acute stimulation with LPS. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP)alpha, peroxisome proliferator-activated receptor (PPAR)gamma and S100A1 were maximal during adipocyte differentiation and then significantly decreased. The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells. The mRNA levels and secretion of adiponectin, quickly rose as adipocytes matured and then declined. The mRNA levels of IL6, as well as its secretion, increased as preadipocytes matured and became old cells; a similar trend was also found for MCP-1. LPS decreased the mRNA levels of C/EBP alpha and PPAR gamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin. LPS significantly increased the mRNA levels of IL-6, as well as its secretion, with a similar trend also observed for MCP-1. These data suggest that aging adipocytes in vitro show a decline in pro-adipogenic signals, in genes involved in glucose metabolism and cytoskeleton maintenance and in adiponectin. These changes are paralleled by an increase in inflammatory cytokines; inflammation seems to mimic and amplify the effects of cellular aging on adipocytes.