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, DGKε resides in the ER. This study examined how DGKε is implicated in signal transduction and lipid homeostasis. DGKε-deficient mice were fed a high-fat diet (HFD) for 40 d. We observed that DGKε 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 DGKε 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 ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes.
Keywords: PKC; adipose triglyceride lipase; hormone-sensitive lipase; lipid droplet; type 2 diabetes.