| First Author | Nakano T | Year | 2020 |
| Journal | Adv Biol Regul | Volume | 75 |
| Pages | 100659 | PubMed ID | 31607681 |
| Mgi Jnum | J:301906 | Mgi Id | MGI:6507275 |
| Doi | 10.1016/j.jbior.2019.100659 | Citation | Nakano T, et al. (2020) Mice lacking DGKepsilon show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner. Adv Biol Regul 75:100659 |
| abstractText | Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. DG kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Consequently, DGK plays a pivotal role in the control of lipid metabolism and signal transduction pathway. Recently, a report has described that DGKepsilon-knockout (KO) mice show expansion of epididymal white adipose tissue (WAT) together with the impairment of glucose clearance after short-term (40 days) high fat diet (HFD) feeding, an early presymptomatic phase of obesity in wild-type animals. Nevertheless, no report describes an investigation of their phenotype under long-term HFD feeding conditions. Remarkably, results obtained during long-term HFD feeding show that WAT mass is decreased significantly and that the blood glucose profile in response to glucose challenge is improved in DGKepsilon-KO mice compared with wild-type, which contrast sharply against the phenotype shown for short-term HFD feeding. Morphological examination reveals that cyclooxygenase-2 (COX-2) expression and clusters of uncoupling protein 1 (UCP1)-positive multilocular brown-like ("beige") adipocyte are induced in DGKepsilon-deficient WAT after long-term HFD feeding, suggesting that beige adipocytes facilitate energy expenditure during prolonged HFD feeding. Administration of celecoxib, a selective inhibitor of COX-2, abolishes the appearance of UCP1-positive beige adipocytes in DGKepsilon-KO mice. These findings suggest that DGKepsilon deficiency promotes visceral WAT remodeling in a COX-2-dependent manner under long-term HFD feeding conditions. |
