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Obesity and Hypertriglyceridemia Produce Cognitive Impairment
Open accessAbstract
Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk (no triglycerides), impaired maintenance of the N-methyl-d-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-d-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain.
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“Obesity and hypertriglyceridemia produce cognitive impairment in mice, including reduced lever pressing for food reward ([59](#B59)), and epidemiological studies show an association of body mass index and risk of Parkinson disease and cognitive decline ([85](#B85)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [59]
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“For example, it has been shown that direct administration of triglycerides can impair hippocampal longterm potentiation, and lowering triglycerides pharmacologically with gemfibrozil can reduce the expression ofmarkers of oxidative stress in the brains of obese mice (Farr et al., 2008).”
Neurological consequences of obesity
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Metadata
- Authors
- Farr, S. A., Yamada, K. A., Butterfield, D. A., Abdul, H. M., Xu, L., Miller, N. E., Banks, W. A., & Morley, J. E.
- Affiliations
- St. Louis VA Medical Center (US)
- Washington University in St. Louis (US)
- University of Kentucky (US)
- Department of Chemistry and Center of Membrane Sciences (D.A.B., H.M.A.), University of Kentucky, Lexington, Kentucky 40536
- Division of Geriatric Medicine (S.A.F., N.E.M., W.A.B., J.E.M.), Saint Louis University School of Medicine, St. Louis, Missouri 63104
- Corresponding author
- Banks, William A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-02-14
- Volume
- 149
- Issue
- 5
- Pages
- 2628-2636
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2329289
- OpenAlex
- W2146978742
- Cited by
- 382
- References
- 37
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 13 · 2023: 17 · 2022: 23 · 2021: 23 · 2020: 21 · 2019: 20 · 2018: 26 · 2017: 26 · 2016: 34 · 2015: 27 · 2014: 29 · 2013: 24 · 2012: 20
- FWCI
- 9.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- U.S. Public Health Service (051334, 42774)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity, hypertriglyceridemia, cognitive impairment, triglycerides, metabolic syndrome X, leptin resistance, dyslipidemia, gemfibrozil, triolein, palmitate, NMDA receptor, hippocampal long-term potentiation, oxidative stress, avoidance learning, Morris water maze, food reward
- MeSH terms
- Animals, Hypolipidemic Agents, Avoidance Learning, Cognition Disorders, Diet, Atherogenic, Male, Memory, Mice, Inbred Strains, Obesity, Swimming, Triolein, Lipid Peroxidation, Hypertriglyceridemia, Gemfibrozil, Maze Learning, Excitatory Postsynaptic Potentials, Mice
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