Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice.
Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice.
复制标题
DOI：
10.1186/s12979-022-00323-7
复制
发表时间：
2022-12-22
影响因子：
7.9
通讯作者：
Feldman, Eva L.
中科院分区：
文献类型：
--
作者：
Henn, Rosemary E.;Elzinga, Sarah E.;Glass, Emily;Parent, Rachel;Guo, Kai;Allouch, Adam A.;Mendelson, Faye E.;Hayes, John;Webber-Davis, Ian;Murphy, Geoffery G.;Hur, Junguk;Feldman, Eva L.
肥胖率在全球范围内都在上升。肥胖会导致许多并发症，包括随着年龄的增长易患上认知障碍。免疫失调，包括炎症(如循环细胞因子增加)和免疫衰老(免疫系统功能下降)，通常发生在肥胖和衰老中，并可能影响认知功能。因此，一生中免疫系统的变化可能会影响肥胖对神经炎症和相关认知障碍的影响。然而，年龄在肥胖引起的神经炎症和认知障碍中的作用尚不清楚。为了进一步确定这种假定的关系，目前的研究使用高脂饮食(HFD)肥胖的小鼠模型，检查了代谢和炎症特征，以及认知变化。首先，HFD促进了与年龄相关的海马区基因表达的变化。考虑到这种早期HFD诱导的衰老表型，我们给年轻成年和中年小鼠喂饲HFD，以确定年龄对炎症反应、代谢特征和认知功能的影响。正如预期的那样，HFD导致两个年龄组的代谢紊乱表型。然而，老年加剧了HFD的认知和神经炎性变化，并对海马炎性基因的表达进行了双向调节。总而言之，这些数据表明，HFD促进了大脑中的一种早期衰老表型，这提示了炎症和免疫衰老。此外，年龄显著增加了HFD对认知结果和大脑中神经炎性程序调节的影响。网上版载有补充材料，可在10.1186/s12979-022-00323-7查阅。
Obesity rates are increasing worldwide. Obesity leads to many complications, including predisposing individuals to the development of cognitive impairment as they age. Immune dysregulation, including inflammaging (e.g., increased circulating cytokines) and immunosenescence (declining immune system function), commonly occur in obesity and aging and may impact cognitive impairment. As such, immune system changes across the lifespan may impact the effects of obesity on neuroinflammation and associated cognitive impairment. However, the role of age in obesity-induced neuroinflammation and cognitive impairment is unclear. To further define this putative relationship, the current study examined metabolic and inflammatory profiles, along with cognitive changes using a high-fat diet (HFD) mouse model of obesity. First, HFD promoted age-related changes in hippocampal gene expression. Given this early HFD-induced aging phenotype, we fed HFD to young adult and middle-aged mice to determine the effect of age on inflammatory responses, metabolic profile, and cognitive function. As anticipated, HFD caused a dysmetabolic phenotype in both age groups. However, older age exacerbated HFD cognitive and neuroinflammatory changes, with a bi-directional regulation of hippocampal inflammatory gene expression. Collectively, these data indicate that HFD promotes an early aging phenotype in the brain, which is suggestive of inflammaging and immunosenescence. Furthermore, age significantly compounded the impact of HFD on cognitive outcomes and on the regulation of neuroinflammatory programs in the brain. The online version contains supplementary material available at 10.1186/s12979-022-00323-7.
登录
查看更多内容
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
3.7
作者：
Barron AM;Rosario ER;Elteriefi R;Pike CJ
通讯作者：
Pike CJ
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
5.3
作者：
Cope, Elise C.;LaMarca, Elizabeth A.;Gould, Elizabeth
通讯作者：
Gould, Elizabeth
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K