Neurobiol Aging 2019 May 3; 80:154-172
AG051496,AG049050,AG10133,AG19771,AG024904, for additional funding information please see publication
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.
Graham, Leah C.; Grabowska, Weronika; Chun, Yoona; Risacher, Shannon L; Philip, Vivek M.; Saykin, Andrew J; Neuroimaging Initiative, Alzheimer's Disease; Sukoff Rizzo, Stacey J; and Howell, Gareth R, "Exercise prevents obesity-induced cognitive decline and white matter damage in mice." (2019). Faculty Research 2019. 134.