Gilham Dean, Perreault Kathleen R, Holmes Charles F B, Brindley David N, Vance Dennis E, Lehner Richard
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Biochim Biophys Acta. 2005 Oct 1;1736(3):189-99. doi: 10.1016/j.bbalip.2005.08.013. Epub 2005 Sep 2.
It is recognized that the majority of very low density lipoprotein (VLDL) associated triacylglycerol (TG) is synthesized from fatty acids and partial acylglycerols generated by lipolysis of intra-hepatic storage rather than made de novo. Triacylglycerol hydrolase (TGH) is involved in mobilizing stored TG. Modulating the ability of TGH to hydrolyze stored lipids represents a potentially regulated and rate limiting step in VLDL assembly. Phosphorylation of lipases and carboxylesterases trigger diverse but functionally significant events. We explored the potential for regulating the mobilization of hepatic TG through phosphorylation of TGH. Insulin is known to suppress VLDL secretion from liver, and glucagon can be considered an opposing hormone. However, neither insulin nor glucagon treatment of hepatocytes led to phosphorylation of TGH or changes in its activity. Augmenting intracellular TG stores by incubations with oleic acid also did not lead to changes in TGH activity. Therefore, changes in phosphorylation state are not a mechanism for regulating TGH activity, access to TG substrate pools or for TGH-mediated contributions to VLDL assembly and secretion.
人们认识到，大多数与极低密度脂蛋白（VLDL）相关的三酰甘油（TG）是由肝内储存的脂肪分解产生的脂肪酸和部分酰基甘油合成的，而非从头合成。三酰甘油水解酶（TGH）参与动员储存的TG。调节TGH水解储存脂质的能力是VLDL组装中一个潜在的受调控且限速的步骤。脂肪酶和羧酸酯酶的磷酸化引发了多样但功能上重要的事件。我们探究了通过TGH磷酸化来调节肝内TG动员的可能性。已知胰岛素会抑制肝脏中VLDL的分泌，而胰高血糖素可被视为一种相反的激素。然而，用胰岛素或胰高血糖素处理肝细胞均未导致TGH磷酸化或其活性改变。用油酸孵育增加细胞内TG储存也未导致TGH活性改变。因此，磷酸化状态的变化不是调节TGH活性、获取TG底物池或TGH对VLDL组装和分泌贡献的机制。
