Document Type

Article

Publication Date

5-3-2019

Keywords

JMG

JAX Source

Neurobiol Aging 2019 May 3; 80:154-172

PMID

31170535

DOI

https://doi.org/10.1016/j.neurobiolaging.2019.03.018

Grant

AG051496,AG049050,AG10133,AG19771,AG024904, for additional funding information please see publication

Abstract

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.

Comments

The authors thank Drs. Simon John, Mimi DeVries, and Jeffrey Harder for western diet development; Keating Pepper for help with IMARIS; Laura Anderson for behavioral phenotyping; Zoe Reifsnyder for figure development; and JohnWest and Yu-ChienWu for help with the imaging analysis.

Open access under Creative Commons Attribution (CC BY) license.

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