title: Obesity increases cerebrocortical reactive oxygen species and impairs brain function.
abstract: Nearly two-thirds of the population in the United States is overweight or obese, and this unprecedented level of obesity will undoubtedly have a profound impact on overall health, although little is currently known about the effects of obesity on the brain. The objective of this study was to investigate cerebral oxidative stress and cognitive decline in the context of diet-induced obesity (DIO). We demonstrate for the first time that DIO induces higher levels of reactive oxygen species (ROS) in the brain and promotes cognitive impairment. Importantly, we also demonstrate for the first time in these studies that both body weight and adiposity are tightly correlated with the level of ROS. Interestingly, ROS were not correlated with cognitive decline in this model. Alterations in the antioxidant/detoxification Nrf2 pathway, superoxide dismutase, and catalase activity levels were not significantly altered in response to DIO. However, a significant impairment in glutathione peroxidase was observed in response to DIO. Taken together, these data demonstrate for the first time that DIO increases the levels of total and individual ROS in the brain and highlight a direct relationship between the amount of adiposity and the level of oxidative stress within the brain. These data have important implications for understanding the negative effects of obesity on the brain and are vital to understanding the role of oxidative stress in mediating the effects of obesity on the brain.
authors.affiliation: Pennington Biomedical Research Center/Louisiana State University System, Baton Rouge, LA 70808, USA.
authors.forename: Linnea R
authors.initials: LR
authors.lastname: Freeman
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Anand
authors.initials: A
authors.lastname: Nair
authors.forename: Kalavathi
authors.initials: K
authors.lastname: Dasuri
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Fernandez-Kim
authors.forename: Annadora J
authors.initials: AJ
authors.lastname: Bruce-Keller
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase