Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span
Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span
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DOI：
10.1189/jlb.0108028
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Dixit, Vishwa Deep
中科院分区：
文献类型：
--
作者：
Dixit, Vishwa Deep
越来越多的证据表明，代谢和免疫系统之间存在紧密的耦合。这种由神经内分泌肽以及许多细胞因子和趋化因子介导的串扰被认为是负责将能量平衡整合到免疫功能。这些神经内分泌-免疫相互作用在慢性正能量平衡状态下增强，如肥胖期间所见，而热量限制（CR）引起的负能量平衡。新出现的证据表明，肥胖可能与免疫缺陷状态和慢性炎症有关，这导致过早死亡的风险增加。在肥胖期间脂肪组织内的扩张的白细胞群体与老化淋巴微环境内的脂肪细胞数量增加之间的直接相互作用可能构成能量平衡变化导致的重要适应性或病理性反应。与肥胖形成鲜明对比的是，CR会导致负能量平衡，并在迄今为止研究的所有物种中强烈影响健康寿命。因此，内源性神经内分泌代谢传感器升高或抑制的结果，在能量平衡的变化可能提供了一个重要的机制，了解抗衰老和潜在的免疫增强CR的性质。Ghrelin是一种负能量平衡的传感器，在肥胖期间减少，并通过CR增加。Ghrelin还通过减少促炎细胞因子调节免疫功能，并促进衰老过程中的胸腺生成，因此，可能是一个新的CR模拟靶点。识别这些促食欲代谢因子所使用的免疫效应和分子途径可以提供潜在的新方法来增强免疫力和增加健康寿命。
Increasing evidence suggests a tight coupling of metabolic and immune systems. This cross-talk mediated by neuroendocrine peptides as well as numerous cytokines and chemokines is believed to be responsible for integrating energy balance to immune function. These neuroendocrine-immune interactions are heightened during the state of chronic positive energy balance, as seen during obesity, and negative energy balance caused by caloric restriction (CR). Emerging evidence suggests that obesity may be associated with an immunodeficient state and chronic inflammation, which contribute to an increased risk of premature death. The direct interactions between expanded leukocyte populations within the adipose tissue during obesity and an increased number of adipocytes within an aging lymphoid microenvironment may constitute an important adaptive or pathological response as a result of change in energy balance. In stark contrast to obesity, CR causes negative energy balance and robustly prolongs a healthy lifespan in all of the species studied to date. Therefore, the endogenous neuroendocrine-metabolic sensors elevated or suppressed as a result of changes in energy balance may offer an important mechanism in understanding the antiaging and potential immune-enhancing nature of CR. Ghrelin, one such sensor of negative energy balance, is reduced during obesity and increased by CR. Ghrelin also regulates immune function by reducing proinflammatory cytokines and promotes thymopoiesis during aging and thus, may be a new CR mimetic target. The identification of immune effects and molecular pathways used by such orexigenic metabolic factors could offer potentially novel approaches to enhance immunity and increase healthy lifespan.