The Jackson Laboratory, Bar Harbor, ME, USA; Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
The Jackson Laboratory, Bar Harbor, ME, USA; College of the Atlantic, Bar Harbor, ME, USA.
Neurobiol Aging. 2019 Aug;80:154-172. doi: 10.1016/j.neurobiolaging.2019.03.018. Epub 2019 May 3.
Obesity in the western world has reached epidemic proportions, and yet the long-term effects on brain health are not well understood. To address this, we performed transcriptional profiling of brain regions from a mouse model of western diet (WD)-induced obesity. Both the cortex and hippocampus from C57BL/6J (B6) mice fed either a WD or a control diet from 2 months of age to 12 months of age (equivalent to midlife in a human population) were profiled. Gene set enrichment analyses predicted that genes involved in myelin generation, inflammation, and cerebrovascular health were differentially expressed in brains from WD-fed compared to control diet-fed mice. White matter damage and cerebrovascular decline were evident in brains from WD-fed mice using immunofluorescence and electron microscopy. At the cellular level, the WD caused an increase in the numbers of oligodendrocytes and myeloid cells suggesting that a WD is perturbing myelin turnover. Encouragingly, cerebrovascular damage and white matter damage were prevented by exercising WD-fed mice despite mice still gaining a significant amount of weight. Collectively, these data show that chronic consumption of a WD in B6 mice causes obesity, neuroinflammation, and cerebrovascular and white matter damage, but these potentially damaging effects can be prevented by modifiable risk factors such as exercise.
西方世界的肥胖问题已经达到了流行的程度，但长期对大脑健康的影响还没有得到很好的理解。为了解决这个问题，我们对一种西方饮食（WD）诱导肥胖的小鼠模型的大脑区域进行了转录谱分析。从 2 个月大到 12 个月大（相当于人类中年），C57BL/6J（B6）小鼠分别用 WD 或对照饮食喂养，我们对其大脑的皮层和海马体进行了分析。基因集富集分析预测，与对照饮食喂养的小鼠相比，WD 喂养的小鼠大脑中与髓鞘生成、炎症和脑血管健康相关的基因表达存在差异。使用免疫荧光和电子显微镜，我们发现 WD 喂养的小鼠大脑中的白质损伤和脑血管退化明显。在细胞水平上，WD 导致少突胶质细胞和髓样细胞数量增加，这表明 WD 扰乱了髓鞘的新陈代谢。令人鼓舞的是，尽管 WD 喂养的小鼠仍然体重显著增加，但锻炼可以预防其脑血管损伤和白质损伤。总的来说，这些数据表明，慢性摄入 WD 会导致 B6 小鼠肥胖、神经炎症以及脑血管和白质损伤，但这些潜在的有害影响可以通过可改变的风险因素（如锻炼）来预防。
