CD36
巨噬细胞
过剩1
TLR4型
生物
内科学
内分泌学
脂解
酵母多糖
脂肪甘油三酯脂肪酶
葡萄糖摄取
细胞生物学
生物化学
信号转导
脂肪组织
基因
体外
胰岛素
医学
作者
Kenneth R. Feingold,Judy K. Shigenaga,Mahmood R. Kazemi,Carol M. McDonald,Sophie Patzek,Andrew S. Cross,Arthur H. Moser,Carl Grünfeld
摘要
Abstract TLR activation by multiple pathways leads to triglyceride accumulation in macrophages that could contribute to the accelerated atherosclerosis seen in chronic infections and inflammatory diseases. LPS treatment of macrophages induces TG accumulation, which is accentuated by TG-rich lipoproteins or FFA. We defined pathways altered during macrophage activation that contribute to TG accumulation. Glucose uptake increased with activation, accompanied by increased GLUT1. Oxidation of glucose markedly decreased, whereas incorporation of glucose-derived carbon into FA and sterols increased. Macrophage activation also increased uptake of FFA, associated with an increase in CD36. Oxidation of FA was markedly reduced, whereas the incorporation of FA into TGs increased, associated with increased GPAT3 and DGAT2. Additionally, macrophage activation decreased TG lipolysis; however, expression of ATGL or HSL was not altered. Macrophage activation altered gene expression similarly when incubated with exogenous FA or AcLDL. Whereas activation with ligands of TLR2 (zymosan), TLR3 (poly I:C), or TLR4 (LPS) induced alterations in macrophage gene expression, leading to TG accumulation, treatment of macrophages with cytokines had minimal effects. Thus, activation of TLRs leads to accumulation of TG in macrophages by multiple pathways that may have beneficial effects in host defense but could contribute to the accelerated atherosclerosis in chronic infections and inflammatory diseases.
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