Adiponectin reduces lipid accumulation in macrophage foam cells
Adiponectin reduces lipid accumulation in macrophage foam cells
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DOI：
10.1016/j.atherosclerosis.2008.04.011
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发表时间：
2009-01-01
期刊：
影响因子：
5.3
通讯作者：
Fu, Yuchang
中科院分区：
文献类型：
--
作者：
Tian, Ling;Luo, Nanlan;Fu, Yuchang
脂联素是脂肪细胞分泌的几种重要的代谢活性细胞因子之一。在流行病学上，这种脂肪因子的低循环水平与肥胖有关。胰岛素抵抗、11型糖尿病和心血管疾病。为了确定脂联素是否可以调节巨噬细胞的脂质代谢，我们利用慢病毒载体表达系统在人THP-1巨噬细胞泡沫细胞中表达了脂联素基因，并证明了转导脂联素基因的巨噬细胞与转导LacZ基因的对照巨噬细胞相比，脂联素基因转导的巨噬细胞的脂质蓄积减少。转导脂联素基因的巨噬细胞也表现出氧化低密度脂蛋白(OxLDL)摄取减少和高密度脂蛋白介导的胆固醇流出增加。此外，研究表明，这些脂联素转导的巨噬细胞泡沫细胞中脂质积累减少的两种潜在机制。第一个机制涉及PPAR、伽马和LXR信号通路，它们上调ABCA1的表达，促进这些细胞前面的脂质外流。第二种机制包括脂质摄取减少和脂水解增加，这可能导致转化的巨噬细胞泡沫细胞SR-AI降低，SR-BI和HSL基因活性增加。我们还证实了两种致动脉粥样硬化的细胞因子MCP-1和TNF-α的表达。在脂联素转导的巨噬细胞泡沫细胞中，脂联素表达减少，提示脂联素可能通过多种途径调节巨噬细胞的脂代谢。我们的研究为脂联素介导的脂代谢改变和巨噬细胞泡沫细胞形成的潜在机制提供了新的见解，这些改变可能影响动脉粥样硬化的发展。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Adiponectin is one of several, important metabolically active cytokines secreted from adipocytes. Low circulating levels of this adipokine have been associated epidemiologically with obesity. insulin resistance, type 11 diabetes, and cardiovascular disease. To determine if adiponectin can modulate lipid metabolism in macrophages, we expressed the adiponectin gene in human THP-1 macrophage foam Cells using a lentiviral vector expression system and demonstrated that macrophages transduced with the adiponectin gene had decreased lipid accumulation compared with control macrophages transduced with the LacZ gene. Macrophages transduced with the adiponectin gene also exhibited decreased oxidized low-density lipoprotein (oxLDL) uptake and increased HDL-mediated cholesterol efflux.Additional studies Suggest two potential mechanisms for the reduced lipid accumulation in these adiponectin-transduced macrophage foam cells. The first mechanism involves the PPAR gamma and LXR signaling pathways which up-regulate the expression of ABCA1 and promote lipid efflux front these cells. The second mechanism involves decreased lipid uptake and increased lipid hydrolysis which may result front decreased SR-AI and increased SR-BI and HSL gene activities in the transformed macrophage foam cells. We also demonstrated that the expression of two proatherogenic cytokines, MCP-1 and TNF alpha. were decreased in the adiponectin-transduced macrophage foam cells.These results suggest that adiponectin may modulate Multiple pathways of lipid metabolism in macrophages. Our Studies provide new insights into potential mechanisms of adiponectin-mediated alterations in lipid metabolism and macrophage foam cell formation which may impact the development of atherosclerosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.