| First Author | Neels JG | Year | 2006 |
| Journal | Am J Pathol | Volume | 168 |
| Issue | 2 | Pages | 435-44 |
| PubMed ID | 16436658 | Mgi Jnum | J:106303 |
| Mgi Id | MGI:3618016 | Doi | 10.2353/ajpath.2006.050699 |
| Citation | Neels JG, et al. (2006) Autoamplification of tumor necrosis factor-alpha: a potential mechanism for the maintenance of elevated tumor necrosis factor-alpha in male but not female obese mice. Am J Pathol 168(2):435-44 |
| abstractText | Although tumor necrosis factor-alpha (TNF-alpha) is elevated in adipose tissue in obesity and may contribute to the cardiovascular and metabolic risks associated with this condition, the mechanisms leading to elevated TNF-alpha remain elusive. We hypothesized that autoamplification of TNF-alpha contributes to the maintenance of elevated TNF-alpha in obesity. Treatment of 3T3-L1 adipocytes with TNF-alpha, or injection of TNF-alpha into C57BL/6J mice, up-regulated TNF-alpha mRNA in adipocytes and in adipose tissues, respectively. Ob/ob male but not female mice lacking TNF-alpha receptors showed significantly lower levels of adipose TNF-alpha mRNA when compared with TNF-alpha receptor-expressing ob/ob mice. Thus, the lack of endogenous TNF-alpha signaling reduced adipose TNF-alpha mRNA in ob/ob male mice. Additionally, hyperinsulinemia potentiated this TNF-alpha-mediated autoamplification response in adipose tissues and in adipocytes in a synergistic and dose-dependent manner. Studies in which TNF-alpha was injected into lean mice lacking individual TNF-alpha receptors indicated that TNF-alpha autoamplification in adipose tissues was mediated primarily via the p55 TNF-alpha receptor whereas the p75 TNF-alpha receptor appeared to augment this response. Finally, TNF-alpha autoamplification in adipocytes occurred via the protein kinase C signaling pathway and the transcription factor nuclear factor-kappaB. Thus, TNF-alpha can positively autoregulate its own biosynthesis in adipose tissue, contributing to the maintenance of elevated TNF-alpha in obesity. |
