Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration.
Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration.
复制标题
黑皮质素受体的中枢阻断会减弱对外周白细胞介素 1β 给药的代谢和运动反应。
DOI：
10.1016/j.neuropharm.2007.10.014
复制
发表时间：
2008
影响因子：
4.7
通讯作者：
Reyes,TeresaM
中科院分区：
文献类型：
--
作者：
Whitaker,KeithW;Reyes,TeresaM
Loss of appetite and cachexia is an obstacle in the treatment of chronic infection and cancer. Proinflammatory cytokines released from activated immune cells and acting in the central nervous system (CNS) are prime candidates for mediating these metabolic changes, potentially affecting both energy intake as well as energy expenditure. The effect of intravenous administration of two proinflammatory cytokines, interleukin (IL)-1β (15μg/kg) and tumor necrosis factor (TNF)-α (10μg/kg), on food and water intake, locomotor activity, oxygen consumption (VO2), and respiratory exchange ratio (RER) was evaluated. The two cytokines elicited a comparable decrease in food intake and activated similar numbers of cells in the paraventricular nucleus of the hypothalamus (PVH), a region that plays a critical role in the regulation of appetite and metabolism (determined via expression of the immediate early gene, c-fos). However, only IL-1β reduced locomotion and RER, and increased VO2, while TNF-α was without effect. To examine the role of the melanocortins in mediating IL-1β- induced metabolic changes, animals were pretreated centrally with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked the effect of IL-1β on food intake and RER at later time points (beyond 8h post injection), as well as the hypoactivity and increased metabolic rate. Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1β.
