Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes
Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes
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DOI：
10.1096/fj.201701050r
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发表时间：
2018-08-01
期刊：
影响因子：
4.8
通讯作者：
Goto, Kaoru
中科院分区：
文献类型：
--
作者：
Nakano, Tomoyuki;Seino, Keiko;Goto, Kaoru
脂质代谢与信号转导和能量平衡密切相关。过量的热量摄入会导致脂质代谢异常，促进肥胖和胰岛素抵抗。甘油二酯（DG）是内质网（ER）中甘油三酯代谢的第二信使和中间代谢产物。然而，它仍然是不确定的DG在信号和能量稳态的作用是如何在细胞内调节。DG激酶（DGK）是磷酸化DG的酶，其中DGK激酶位于ER中。本研究探讨了DGK β如何参与信号转导和脂质稳态。给DGK ε缺陷小鼠喂食高脂饮食（HFD）40 d。我们观察到，DGK β缺乏促进脂肪细胞中的脂肪积累，随后促进喂食HFD的小鼠的胰岛素抵抗。这种异常的脂肪代谢是由脂解活性的下调介导的，如脂肪甘油三酯脂肪酶和脂肪敏感性脂肪酶。此外，DG敏感性PKC的激活导致脂肪组织的胰岛素抵抗，这可能是由于DG代谢延迟引起的。我们的数据表明，DGK β将第二信使信号系统与脂肪细胞中的能量稳态联系起来，并且其缺乏导致异常脂质代谢，例如肥胖和胰岛素抵抗。Seino，K.，若林岛Stafforini，D. M.，Topham，M. K.，后藤，K.二酰基甘油激酶β的缺失通过降低小鼠脂肪细胞的脂解活性赋予肥胖易感性。
Lipid metabolism is closely involved with signal transduction and energy homeostasis. Excess calorie intake causes abnormal lipid metabolism, promoting obesity and insulin resistance. Diacylglycerol (DG) represents not only a lipidic second messenger but also an intermediate metabolite for triglyceride metabolism in the endoplasmic reticulum (ER). However, it remains undetermined how the roles of DG in signaling and energy homeostasis is regulated within the cell. Of DG kinases (DGKs), which are enzymes that phosphorylate DG, DGK epsilon resides in the ER. This study examined how DGK epsilon is implicated in signal transduction and lipid homeostasis. DGK epsilon-deficient mice were fed a high-fat diet (HFD) for 40 d. We observed that DGK epsilon deficiency promotes fat accumulation in adipocytes and subsequently promotes insulin resistance in mice fed an HFD. This abnormal fat metabolism is mediated by down-regulation of lipolytic activities, such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, activation of DG-sensitive PKC leads to insulin resistance in adipose tissue, which may be caused by delayed metabolism of DG. Our data suggest that DGK epsilon links the second messenger signaling system to energy homeostasis in adipocytes and that its deficiency results in abnormal lipid metabolism such as obesity and insulin resistance.Nakano, T., Seino, K., Wakabayashi, I., Stafforini, D. M., Topham, M. K., Goto, K. Deletion of diacylglycerol kinase epsilon confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes.