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J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):290-298. doi: 10.1093/gerona/gly127.

Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline.

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Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program, Oklahoma City.
Barshop Institute for Longevity and Aging Studies and Department of Physiology, University of Texas Health Science Center at San Antonio.
Division of Neonatology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
Oklahoma City VA Medical Center, Oklahoma City.
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City.
Department of Medical Physics and Informatics, University of Szeged, Hungary.
Department of Pulmonology, Semmelweis University, Budapest, Hungary.


There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis that synergistic effects of obesity and aging on inflammatory processes exert deleterious effects on hippocampal function, young and aged C57BL/6 mice were rendered obese by chronic feeding of a high-fat diet followed by assessment of learning and memory function, measurement of hippocampal long-term potentiation (LTP), assessment of changes in hippocampal expression of genes relevant for synaptic function and determination of synaptic density. Because there is increasing evidence that altered production of lipid mediators modulate LTP, neuroinflammation and neurovascular coupling responses, the effects of obesity on hippocampal levels of relevant eicosanoid mediators were also assessed. We found that aging exacerbates obesity-induced microglia activation, which is associated with deficits in hippocampal-dependent learning and memory tests, impaired LTP, decreased synaptic density, and dysregulation of genes involved in regulation of synaptic plasticity. Obesity in aging also resulted in an altered hippocampal eicosanoid profile, including decreases in vasodilator and pro-LTP epoxy-eicosatrienoic acids (EETs). Collectively, our results taken together with previous findings suggest that obesity in aging promotes hippocampal inflammation, which in turn may contribute to synaptic dysfunction and cognitive impairment.


Inflammaging; Metabolic syndrome; Mild cognitive impairment; VCI; Vascular cognitive impairment

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