| First Author | Tu TH | Year | 2015 |
| Journal | FEBS J | Volume | 282 |
| Issue | 8 | Pages | 1468-80 |
| PubMed ID | 25691217 | Mgi Jnum | J:237323 |
| Mgi Id | MGI:5811981 | Doi | 10.1111/febs.13236 |
| Citation | Tu TH, et al. (2015) 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages. FEBS J 282(8):1468-80 |
| abstractText | Obesity-induced monocyte/macrophage proliferation and activation play a crucial role in various chronic inflammatory metabolic disorders, such as insulin resistance, diabetes mellitus, and atherosclerosis. 4-1BBL, a member of the tumor necrosis factor superfamily expressed on monocytes/macrophages, provides inflammatory signals to modulate their proliferation, survival, and cytokine release. Previously, we demonstrated that 4-1BBL signaling promotes adipose inflammation through enhancement of macrophage activation. Here, we show that 4-1BBL stimulation on monocytes/macrophages enhanced reprogramming of glucose metabolism in the cells, and that this was accompanied by cell proliferation. 4-1BBL stimulation on macrophages increased glucose uptake, transcript/protein levels of glucose transporter 1 and glycolytic enzymes, and lactate production. It also enhanced transcript levels of genes involved in the pentose phosphate pathway and lipogenesis. The 4-1BBL-induced metabolic reprogramming was mediated by AKT-mammalian target of rapamycin signaling. The effect of 4-1BBL-induced macrophage proliferation was completely abolished by 2-deoxyglucose, a glycolytic inhibitor. These findings suggest that 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages to support their energy demands and biomass production. The 4-1BBL signaling pathway may be a valid target for controlling macrophage-mediated chronic inflammation in obesity and metabolic diseases. |
