Fatty acid transport in adipocytes and the development of insulin resistance.
Fatty acid transport in adipocytes and the development of insulin resistance.
复制标题
脂肪细胞中的脂肪酸转运和胰岛素抵抗的发展。
DOI：
10.1002/9780470985571.ch10
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发表时间：
2007
影响因子：
--
通讯作者：
Bernlohr,DavidA
中科院分区：
文献类型：
--
作者：
Lobo,Sandra;Bernlohr,DavidA
脂肪酸进入脂肪细胞是一个复杂的多因素过程，由生化和生物物理过程驱动，将跨膜通量与依赖于ATP的脂肪酸酯化联系起来。与游离脂肪酸(FFA)内流有关的脂肪细胞蛋白包括CD36作为一般脂质受体，小窝蛋白1作为内吞/吐出囊泡周期的组成部分，以及催化脂类酯化生成酰基辅酶A的合成酶(FATP1，ACSL1)。在脂肪细胞中，CD36、ACSL1和FATP1在胰岛素的响应下从细胞内位置转移到质膜，从而定位这些关键蛋白以促进FFA酯化。慢病毒携带针对FATP1的shRNA进入3T3-L1脂肪细胞，导致胰岛素刺激的FFA摄取完全丧失，TAG/DAG/MAG的积聚减少，并增强胰岛素刺激的2-脱氧葡萄糖摄取。在FATP1基因敲除的脂肪细胞中，胰岛素刺激的己糖摄取增加与酪氨酸磷酸化增加和IRS1蛋白丰富相关。对与胰岛素信号转导有关的脂质激活的丝氨酸激酶的研究表明，在FATP1基因敲除的脂肪细胞中，S6K和JNK1的丰度或磷酸化没有改变，但PKCθ的磷酸化和IKKα/β的丰度显著降低。这些结果表明，脂肪细胞中的脂滴池在调节控制胰岛素作用的激酶级联反应中起着主要作用。
Fatty acid influx into adipocytes is a complex multifactoral process driven by biochemical and biophysical processes linking transmembrane flux to the ATP‐dependent esterification of fatty acids. Adipocyte proteins implicated in free fatty acid (FFA) influx include CD36 functioning as a general lipid receptor, caveolin 1 functioning as a component of an endocytotic/exocytotic vesicular cycle and the acyl CoA synthetases (FATP1, ACSL1) catalysing esterification of lipids producing acyl CoAs. In adipocytes, CD36, ACSL1 and FATP1 translocate from intracellular sites to the plasma membrane in response to insulin thereby positioning these key proteins to facilitate FFA esterification. Lentiviral delivery of shRNA targeting FATP1 in 3T3‐L1 adipocytes results in a complete loss of insulin‐stimulated FFA uptake, decreased accumulation of TAG/DAG/MAG and potentiated insulin‐stimulated 2‐deoxyglucose uptake. Increased insulin‐stimulated hexose uptake in FATP1 knockdown adipocytes is correlated with increased tyrosine phosphorylation and abundance of IRS1 protein. Evaluation of the lipid activated serine kinases implicated in insulin signalling reveals that S6K and JNK1 were not altered in abundance or phosphorylation in FATP1 knockdown adipocytes but that the phosphorylation of PKCθ and abundance of IKKα/β were significantly reduced. These results suggest lipid droplet pools in the adipocyte play a major role in regulating kinase cascades controlling insulin action.