Hu Liping, Deeney Jude T, Nolan Christopher J, Peyot Marie-Line, Ao Ada, Richard Ann Marie, Luc Esthere, Faergeman Nils J, Knudsen Jens, Guo Wen, Sorhede-Winzell Maria, Prentki Marc, Corkey Barbara E
Obesity Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1085-92. doi: 10.1152/ajpendo.00210.2005. Epub 2005 Aug 9.
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 microM) 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.
细胞内脂解是脂质代谢的主要途径，不仅在提供游离脂肪酸作为能量底物方面发挥作用，还在细胞内信号转导中起作用。后者可能在胰岛β细胞胰岛素分泌的调节中尤为重要。因此，脂解在不同组织中的调节机制备受关注。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微摩尔）刺激正常小鼠和激素敏感脂肪酶（HSL）基因敲除小鼠的胰岛以及经磷酸酶处理的胰岛中的脂肪酶活性，表明这种刺激作用既不依赖于HSL，也不依赖于磷酸化。相反，我们重现了之前发表的观察结果，即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。相比之下，ACBP阻断了对胰岛脂肪酶活性的刺激作用，推测是由于LC-CoA的结合和隔离。这些数据表明，在脂肪酸代谢、LC-CoA信号传导和脂解方面，胰岛和脂肪细胞之间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脂肪从脂肪细胞的释放并通过胰岛素作用促进脂肪储存来降低循环脂肪。
