Abstract
Diacylglycerol (DG) is unique in lipid metabolism because it serves not only as an intermediate product for triglyceride synthesis, but also as a signaling molecule that activates proteins containing DG-responsive elements, such as protein kinase C. Consequently, DG acts as a hub between energy metabolism and intracellular signaling. Of DG metabolizing pathways, DG kinase (DGK) phosphorylates DG to produce phosphatidic acid, which also serves as a second messenger. Several lines of evidence suggest that DGK is deeply involved in metabolic diseases such as obesity and insulin resistance. Of DGK isozymes, DGKε is simplest in terms of structure, but it is characterized by substrate specificity toward arachidonoyl-DG. Recently, we have reported that DGKε deficiency promotes adipose tissue remodeling in mice during the course of high fat diet (HFD) feeding regimen including obesity, insulin resistance, and beige adipogenesis. DGKε ablation engenders altered expression of other lipid metabolizing enzymes, including adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and diacylglycerol acyltransferase (DGAT). Subcellular localization of DGKε in the endoplasmic reticulum suggests involvement of this isozyme in lipid energy homeostasis. This review presents current findings of DGKε in lipid-orchestrated pathophysiology, especially unique phenotypes of DGKε-knockout mice in the early and late stages of obesogenic conditions.
Highlights
Lipid is an indispensable constituent of cells
It must be described that other insulin-reactive organs such as liver and skeletal muscle of DGKε-KO mice exhibit no changes in protein kinase C (PKC) and Akt/PKB expression and activation status, suggesting that insulin signaling is disturbed in adipose tissues of DGKε-KO mice under short-term high fat diet (HFD) feeding conditions
High fat diet studies reveal that under long-term (90 days ∼) HFD feeding conditions, beige adipogenesis is induced in white adipose tissue, which may contribute to enhanced glucose tolerance in DGKε-KO mice
Summary
Lipid is an indispensable constituent of cells. It composes biological membranes surrounding the cell itself, the nucleus, and subcellular organelles. Diacylglycerol (DG), a basic structure of phospholipids, comprises at least 50 molecular species (Sakane et al, 2018) containing two acyl chains of various combinations at sn-1,2, sn-1,3, or sn-2,3 positions (Zechner et al, 2012). In terms of energy metabolism, DG-containing acyl chains at sn-1 and sn-2 positions (1,2-DG) serves as an intermediate product for triglyceride (TG) synthesis. In terms of signal transduction, 1,2-DG is known to serve as an intracellular signaling molecule that activates several proteins including conventional and novel types of protein kinase C (PKC), Unc-13, RasGRP, and transient receptor potential channels (Kanoh et al, 1990; Nishizuka, 1992; Sakane et al, 2007; Goto et al, 2014). DG acts as a hub between lipid metabolism and intracellular signaling
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
