Amaral Maria E, Barbuio Raquel, Milanski Marciane, Romanatto Talita, Barbosa Helena C, Nadruz Wilson, Bertolo Manoel B, Boschero Antonio C, Saad Mario J A, Franchini Kleber G, Velloso Licio A
Department of Internal Medicine, State University of Campinas, Sao Paulo, Brazil.
J Neurochem. 2006 Jul;98(1):203-12. doi: 10.1111/j.1471-4159.2006.03857.x. Epub 2006 Apr 21.
Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.
已知肿瘤坏死因子-α（TNF-α）参与伴随癌症和严重传染病出现的消瘦综合征。最近，已表明TNF-α在2型糖尿病和肥胖症的发病机制中发挥作用。TNF-α对能量储备控制所施加的许多调节作用取决于其对下丘脑的作用。在本研究中，我们表明TNF-α激活大鼠下丘脑的经典促炎信号转导途径。这些信号事件分别导致早期反应基因的转录激活以及细胞因子和细胞因子反应蛋白（如白细胞介素-1β、白细胞介素-6、白细胞介素-10和细胞因子信号转导抑制因子-3）表达的诱导。此外，TNF-α诱导参与进食和产热控制的神经递质的表达。因此，TNF-α可能直接在下丘脑中起作用，诱导促炎反应并调节参与能量稳态的神经递质的表达。
