Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes

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, DGKe resides in the ER. This study examined how DGKe is implicated in signal transduction and lipid homeostasis. DGKe-deficient mice were fed a high-fat diet (HFD) for 40 d. We observed that DGKe deficiency promotes fat accumulation in adipocytes and subsequently promotes insulin resistance in mice fed a 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...