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

Leah C. Graham, Weronika A. Grabowska, Yoona Chun, Shannon L. Risacher, Vivek M. Philip, Andrew J. Saykin, Stacey J. Sukoff Rizzo, Gareth R. Howell

Research output: Contribution to journalArticle

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)154-172
Number of pages19
JournalNeurobiology of Aging
StatePublished - Aug 2019


  • Aging
  • Brain Health
  • Cerebrovascular Health
  • Exercise
  • Neuroinflammation
  • Obesity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of 'Exercise prevents obesity-induced cognitive decline and white matter damage in mice'. Together they form a unique fingerprint.

  • Cite this

    Graham, L. C., Grabowska, W. A., Chun, Y., Risacher, S. L., Philip, V. M., Saykin, A. J., Sukoff Rizzo, S. J., & Howell, G. R. (2019). Exercise prevents obesity-induced cognitive decline and white matter damage in mice. Neurobiology of Aging, 80, 154-172. https://doi.org/10.1016/j.neurobiolaging.2019.03.018