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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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“As insulin resistance was found to be positively correlated with mean escape latency, they suggested that fructose-induced peripheral insulin resistance may contribute to hippocampal-dependent cognitive function, either because chronic hyperinsulinemia might determine a reduced insulin transport into the brain or beca…”
BackgroundMembrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity
García‐Morales, V., Montero, F., González‐Forero, D., Bey, G. R., Gomez-Perez, L. J., Medialdea-Wandossell, M. J., Domínguez-Vías, G., García‐Verdugo, J. M., & Moreno‐López, B. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002153 · Cited by 83
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BackgroundThe emerging role of dietary fructose in obesity and cognitive decline
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“tion of TGs directly into the brain impairs memory [124].”
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Self-citationMetabolic Syndrome, Mild Cognitive Impairment and Dementia
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“Although a high-fat/ high-sucrose diet causes insulin resistance and reduction in learning and memory in Sprague-Dawley rats (Stranahan et al., 2008) and CD1 mice (Farr et al., 2008), this is not the case for C57BL/6 mice (Mielke et al., 2006; Pistell et al., 2010).”
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“…(Elias et al., 2003; Waldstein and Katzel, 2006; Smith et al., 2011) and rodents (Winocur et al., 2005; Farr et al., 2008), and improved cognitive performance following dietary interventions (Farr et al., 2008; Cohen et al., 2011; Leidy et al., 2015) and physical exercise (Smith et al., 2010).”
InfluentialFarr, S. A., Niehoff, M. L., Ceddia, M. A., Herrlinger, K. A., Lewis, B., Feng, S., Welleford, A. S., Butterfield, D. A., & Morley, J. E. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.08.013 · Cited by 68
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“Human obesity continues to increase [1], associated with consumption of high-fat diets; both obesity and high fat consumption are linked to cognitive impairment [2-12] and causal factors for the current type 2 diabetes mellitus (T2DM) pandemic [13].”
BackgroundRemembering to eat: hippocampal regulation of meal onset
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“, 2015; South and Huang, 2008), reduced cognitive function (Farr et al., 2008), and increased impulsivity (Adams et al.”
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Obesity and episodic memory function
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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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