Aging up-regulates expression of inflammatory mediators in mouse adipose tissue
Aging up-regulates expression of inflammatory mediators in mouse adipose tissue
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DOI：
10.4049/jimmunol.179.7.4829
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Meydani, Simin Nikbin
中科院分区：
文献类型：
--
作者：
Wu, Dayong;Ren, Zhihong;Meydani, Simin Nikbin
肥胖是2型糖尿病（T2D）的主要危险因素。衰老与T2D发病率的增加有关，这并不能完全解释为老年人肥胖患病率低得多。脂肪组织（AT）的低度炎症有助于胰岛素抵抗和T2D。因此，我们确定炎症反应是否随着年龄的增长而上调。结果。老龄C57BL小鼠内脏AT的促炎因子IL-1 β、IL-6、tnf - α和COX-2 mRNA表达显著高于年轻小鼠，抗炎因子ppar - γ mRNA表达显著低于年轻小鼠。我们进一步表明，脂肪细胞（AD）而不是包括巨噬细胞（M phi）在内的间质血管细胞是导致老年AT炎症状态升高的细胞，这表明年龄相关的AT炎症增加与肥胖不同，在肥胖中，M phi是主要因素。然而，与年轻的ad条件培养基相比，老年ad条件培养基中培养后，无论年龄（年轻或年老）的腹膜M - phi产生更多的TNF-a和IL-6。这表明，老年小鼠的AD除了产生更多的炎症细胞因子外，还会在其他细胞中引起更高的炎症反应。老年AD患者鞘脂神经酰胺高于年轻AD患者。降低神经酰胺水平或抑制NF-kappa B激活会减少细胞因子的产生，而神经酰胺的添加会使年轻AD的细胞因子产生增加到与老年AD相当的水平，这表明神经酰胺诱导的NF-kappa B激活在AT炎症中起关键作用。
Obesity is a leading risk factor for type 2 diabetes (T2D). Aging is associated with an increase in T2D incidence, which is not totally explained by the much lower prevalence of obesity in the elderly. Low-grade inflammation in adipose tissue (AT) contributes to insulin resistance and T2D. Thus, we determined whether inflammatory responses are up-regulated with age in AT. The results. showed that visceral AT from old C57BL mice had significantly higher mRNA expression of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha, and COX-2 and lower expression of anti-inflammatory PPAR-gamma than those of young mice. We further showed that adipocytes (AD) and not stromal vascular cells including macrophages (M phi) were the cells responsible for this higher inflammatory state of the aged AT, suggesting that the age-associated increase in AT inflammation is distinguished from that seen in obesity, in which M phi are the main contributors. However, peritoneal M phi of either age (young or old) produced more TNF-a and IL-6 after incubation in old AD-conditioned medium compared with young AD-conditioned medium. This suggests that in addition to producing more inflammatory cytokines, AD from old mice induce a higher inflammatory response in other cells. Sphingolipid ceramide was higher in old compared with young AD. Reducing ceramide levels or inhibiting NF-kappa B activation decreased cytokine production, whereas the addition of ceramide increased cytokine production in young AD to a level comparable to that seen in old AD, suggesting that ceramide-induced activation of NF-kappa B plays a key role in AT inflammation.