Cited by 382Regulation of Appetite and ObesityFatty Acid Research and HealthAdipokines, Inflammation, and Metabolic Diseases

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Obesity and Hypertriglyceridemia Produce Cognitive Impairment

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Farr, Susan A., Yamada, Kelvin A., Butterfield, D. Allan, Abdul, H. Mohammad, Xu, Lin, Miller, Nicole E., Banks, William A., Morley, John E.·2008·Endocrinology

DOI 10.1210/en.2007-1722PMC PMC2329289

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Abstract

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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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.
ORCID: Farr, Susan A.
Butterfield, D. Allan
Xu, Lin
Banks, William A.
Morley, John E.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2008-02-14
Volume: 149
Issue: 5
Pages: 2628-2636
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2007-1722
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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Obesity and Hypertriglyceridemia Produce Cognitive Impairment

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