Exercise prevents obesity-induced cognitive decline and white matter damage in mice

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.

Keywords: Aging; Brain Health; Cerebrovascular Health; Exercise; Neuroinflammation; Obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / prevention & control*
  • Exercise / physiology*
  • Humans
  • Inflammation
  • Leukoencephalopathies / pathology
  • Leukoencephalopathies / prevention & control*
  • Mice, Inbred C57BL
  • Obesity / complications*
  • Obesity / prevention & control
  • Oligodendroglia / pathology
  • Physical Conditioning, Animal / physiology*
  • White Matter / cytology
  • White Matter / pathology