Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice
Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice
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DOI：
10.1016/j.bbi.2015.07.008
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Jin A Shin;Sae Im Jeong;Minsuk Kim;J. Yoon;Hee-Sun Kim;E. Park
中科院分区：
文献类型：
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作者：
Jin A Shin;Sae Im Jeong;Minsuk Kim;J. Yoon;Hee-Sun Kim;E. Park
内脏脂肪组织随着年龄的增长而积累。内脏脂肪的增加伴随着低度炎症与几种成人发病的疾病有关。然而，内脏脂肪组织炎症对老年人正常和缺血脑的影响尚不清楚。为了研究内脏脂肪组织炎症的作用，我们评估了与年轻小鼠（2.5个月）相比，接受假手术或内脏脂肪切除手术的老年雄性小鼠（20个月）血清、内脏脂肪组织和脑中的炎性细胞因子以及血脑屏障（BBB）通透性。此外，缺血性脑损伤进行了比较，在年轻和老年小鼠与假手术和内脏脂肪去除手术。与年轻小鼠相比，老年小鼠检查器官中的白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α水平升高，而内脏脂肪去除小鼠中这些水平降低。老年假手术小鼠血脑屏障通透性增加，紧密连接蛋白表达减少，内脏脂肪去除小鼠也减少。在局灶性缺血损伤后，与假手术小鼠相比，去除内脏脂肪的老年小鼠表现出梗死体积、BBB通透性和缺血脑中促炎细胞因子水平的降低，尽管神经学结局没有显著改善。此外，在内脏脂肪去除的小鼠中，响应于缺血性脑损伤的进一步上调的内脏脂肪组织炎症减弱。这些结果表明，内脏脂肪组织炎症与脑的年龄相关性变化有关，并有助于老年小鼠缺血性脑损伤。我们认为，内脏肥胖应被视为一个因素，影响脑健康和缺血性脑损伤的老年人口。
Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood–brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.