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.
Highlights
Obesity is a major health concern throughout the western world because of its strong association with diseases such as cardiovascular disease, diabetes and dementias
Data was collected nightly (16hrs), analyzed and average distance ran per night/mouse calculated. 139 Behavioral battery The Jackson Laboratory’s Mouse NeuroBehavioral Facility (MNBF) performed the behavioral tasks, with the exception of nest construction and burrowing that were assessed in the Howell lab as reported previously (Deacon, 2012)
The long-term effects of a WD and sedentary lifestyle are of great interest to better understand the environmental risk factors for age-related cognitive decline, dementias and other neurodegenerative diseases
Summary
Obesity is a major health concern throughout the western world because of its strong association with diseases such as cardiovascular disease, diabetes and dementias. Diseases that are influenced by diet and obesity are the greatest cause of morbidity and mortality in the western world, including the United States (Organization, 2009). Studies show that obesity and high fat diets cause cognitive dysfunction in both humans and mice even when controlling for cognitive aging (Elias et al, 2005; Kanoski and Davidson, 2011; Naderali et al, 2009; Pistell et al, 2010). One-third of AD cases, the leading form of dementia globally, is attributed to modifiable risk factors including midlife obesity, physical inactivity, midlife hypertension and type II diabetes (Norton et al.). These risk factors have been strongly associated with non-Alzheimer’s dementias, including vascular dementia (Nguyen et al, 2014). The mechanisms by which high BMI and obesity contribute to cognitive decline and dementias are not understood 3
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
