Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes
Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes
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DOI：
10.1152/ajpendo.00210.2005
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发表时间：
2005-12-01
影响因子：
5.1
通讯作者：
Corkey, BE
中科院分区：
文献类型：
--
作者：
Hu, LP;Deeney, JT;Corkey, BE
细胞内脂肪分解是脂质代谢的主要途径，不仅在提供作为能量底物的游离脂肪酸中起作用，而且在细胞内信号转导中起作用。后者可能在调节胰岛β细胞的胰岛素分泌方面特别重要。因此，在不同组织中调节脂解的机制引起了相当大的兴趣。在此，比较了长链酰基辅酶A酯（LC-CoA）对胰岛和脂肪细胞中脂肪酶活性的影响。棕榈酰辅酶A（Pal-CoA，1-10 μ M）刺激脂肪酶活性在胰岛从正常和脂肪酶敏感脂肪酶（HSL）-null小鼠和磷酸酶处理的胰岛，表明刺激作用既不是对HSL也不是磷酸化依赖。相反，我们复制了先前发表的观察结果，显示LC-CoA在脂肪细胞中抑制HSL活性。LC-CoA对脂肪细胞HSL的抑制作用依赖于磷酸化，并被酰基辅酶A结合蛋白（ACBP）增强。相反，对胰岛脂肪酶活性的刺激作用被ACBP阻断，推测是由于LC-CoA的结合和螯合。这些数据表明胰岛和脂肪细胞之间在脂肪酸代谢、LC-CoA信号传导和脂解方面存在以下组织间关系。胰岛中升高的LC-CoA刺激脂解以产生增加胰岛素分泌的信号，而脂肪细胞中升高的LC-CoA抑制脂解。总之，LC-CoA的这些相反作用通过抑制其从脂肪细胞释放并通过胰岛素作用促进脂肪储存来降低循环脂肪。
Intracellular lipolysis is a major pathway of lipid metabolism that has roles, not only in the provision of free fatty acids as energy substrate, but also in intracellular signal transduction. The latter is likely to be particularly important in the regulation of insulin secretion from islet beta-cells. The mechanisms by which lipolysis is regulated in different tissues is, therefore, of considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA) on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal-CoA, 1-10 mu M) stimulated lipase activity in islets from both normal and hormone-sensitive lipase (HSL)-null mice and in phosphatase-treated islets, indicating that the stimulatory effect was neither on HSL nor phosphorylation dependent. In contrast, we reproduced the previously published observations showing inhibition of HSL activity by LC-CoA in adipocytes. The inhibitory effect of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl-CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase activity was blocked by ACBP, presumably due to binding and sequestration of LC-CoA. These data suggest the following intertissue relationship between islets and adipocytes with respect to fatty acid metabolism, LC-CoA signaling, and lipolysis. Elevated LC-CoA in islets stimulates lipolysis to generate a signal to increase insulin secretion, whereas elevated LC-CoA in adipocytes inhibits lipolysis. Together, these opposite actions of LC-CoA lower circulating fat by inhibiting its release from adipocytes and promoting fat storage via insulin action.