{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:40:05Z","timestamp":1791114005646,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1210\/en.2007-1722","type":"journal-article","created":{"date-parts":[[2008,2,14]],"date-time":"2008-02-14T20:39:43Z","timestamp":1203021583000},"page":"2628-2636","source":"Crossref","is-referenced-by-count":318,"title":["Obesity and Hypertriglyceridemia Produce Cognitive Impairment"],"prefix":"10.1210","volume":"149","author":[{"given":"Susan A.","family":"Farr","sequence":"first","affiliation":[{"name":"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"},{"name":"Geriatrics Research Education and Clinical Center (S.A.F., N.E.M., W.A.B., J.E.M.), Veterans Affairs Medical Center, St. Louis, Missouri 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin A.","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Neurology (K.A.Y., L.X.), Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Allan","family":"Butterfield","sequence":"first","affiliation":[{"name":"Department of Chemistry and Center of Membrane Sciences (D.A.B., H.M.A.), University of Kentucky, Lexington, Kentucky 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Mohammad","family":"Abdul","sequence":"first","affiliation":[{"name":"Department of Chemistry and Center of Membrane Sciences (D.A.B., H.M.A.), University of Kentucky, Lexington, Kentucky 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurology (K.A.Y., L.X.), Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole E.","family":"Miller","sequence":"first","affiliation":[{"name":"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"},{"name":"Geriatrics Research Education and Clinical Center (S.A.F., N.E.M., W.A.B., J.E.M.), Veterans Affairs Medical Center, St. Louis, Missouri 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Banks","sequence":"first","affiliation":[{"name":"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"},{"name":"Geriatrics Research Education and Clinical Center (S.A.F., N.E.M., W.A.B., J.E.M.), Veterans Affairs Medical Center, St. Louis, Missouri 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Morley","sequence":"first","affiliation":[{"name":"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"},{"name":"Geriatrics Research Education and Clinical Center (S.A.F., N.E.M., W.A.B., J.E.M.), Veterans Affairs Medical Center, St. Louis, Missouri 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2008,2,14]]},"reference":[{"key":"2020071612265931800_R1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000082659","article-title":"Interactive effect of obesity indexes on cognition.","volume":"19","author":"Jeong","year":"2005","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2020071612265931800_R2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/sj.ijo.802225","article-title":"Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.","volume":"27","author":"Elias","year":"2003","journal-title":"Int J Obes Relat Metab Disord"},{"key":"2020071612265931800_R3","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/S0140-6736(83)91940-2","article-title":"Cognitive deficiency in obesity independent of social origin.","volume":"14","author":"Sorensen","year":"1983","journal-title":"Lancet"},{"key":"2020071612265931800_R4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/gerona\/59.2.M139","article-title":"The metabolic syndrome and aging","volume":"59A","author":"Morley","year":"2004","journal-title":"J Gerontol Med Sci"},{"key":"2020071612265931800_R5","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1212\/01.WNL.0000158274.31318.3C","article-title":"Impact of plasma lipids and time on memory performance in healthy elderly without dementia.","volume":"64","author":"Reitz","year":"2005","journal-title":"Neurology"},{"key":"2020071612265931800_R6","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1177\/0003319789040004043","article-title":"Reducing hypertriglyceridemia in elderly patients with cerebrovascular disease stabilizes or improves cognition and cerebral perfusion.","volume":"40","author":"Rogers","year":"1989","journal-title":"Angiology"},{"key":"2020071612265931800_R7","doi-asserted-by":"crossref","first-page":"M712","DOI":"10.1093\/gerona\/57.11.M712","article-title":"Plasma HDL levels highly correlate with cognitive function in exceptional longevity","volume":"57","author":"Atmon g, Gabriely","year":"2002","journal-title":"J Gerontol Med Sci"},{"key":"2020071612265931800_R8","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2337\/diabetes.53.5.1253","article-title":"Triglycerides induce leptin resistance at the blood-brain barrier.","volume":"53","author":"Banks","year":"2004","journal-title":"Diabetes"},{"key":"2020071612265931800_R9","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1006\/nlme.1999.3927","article-title":"The effect of cholinergic, GABAergic, serotonergic and glutamatergic receptor modulation on post-trial memory processing in the hippocampus.","volume":"73","author":"Farr","year":"2000","journal-title":"Neurobiol Learn Mem"},{"key":"2020071612265931800_R10","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0006-8993(00)02495-1","article-title":"Permanent and temporary inactivation of the hippocampus impairs T-maze footshock avoidance acquisition and retention.","volume":"872","author":"Farr","year":"2000","journal-title":"Brain Res"},{"key":"2020071612265931800_R11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1212\/WNL.54.2.325","article-title":"Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission.","volume":"54","author":"Thio","year":"2000","journal-title":"Neurology"},{"key":"2020071612265931800_R12","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1126\/science.285.5435.1870","article-title":"Long-term potentiation-a decade of progress?","volume":"285","author":"Malenka","year":"1999","journal-title":"Science"},{"key":"2020071612265931800_R13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.09.012","article-title":"LTP and LTD: an embarrassment of riches.","volume":"44","author":"Malenka","year":"2004","journal-title":"Neuron"},{"key":"2020071612265931800_R14","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.neuroscience.2004.04.046","article-title":"Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain.","volume":"126","author":"Poon","year":"2004","journal-title":"Neuroscience"},{"key":"2020071612265931800_R15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molbrainres.2005.02.020","article-title":"Proteomic identification of less oxidized brain proteins in aged senescence-accelerated mice following administration of antisense oligonucleotide directed at the A\u03b2 region of amyloid precursor protein.","volume":"138","author":"Poon","year":"2005","journal-title":"Mol Brain Res"},{"key":"2020071612265931800_R16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.nbd.2005.11.002","article-title":"Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer\u2019s disease.","volume":"22","author":"Butterfield","year":"2006","journal-title":"Neurobiol Dis"},{"key":"2020071612265931800_R17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/1567205043332162","article-title":"Reactive oxygen and nitrogen species in Alzheimer\u2019s disease.","volume":"1","author":"Aslan","year":"2004","journal-title":"Curr Alzheimer Res"},{"key":"2020071612265931800_R18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/archneur.1974.00490370093018","article-title":"Hyperlipidemic dementia.","volume":"31","author":"Heilman","year":"1974","journal-title":"Arch Neurol"},{"key":"2020071612265931800_R19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1159\/000114761","article-title":"Hyperlipidemia neuropathy and dementia.","volume":"14","author":"Mathew","year":"1976","journal-title":"Eur Neurol"},{"key":"2020071612265931800_R20","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0891-6632(88)80011-4","article-title":"Triglyceride levels affect cognitive function in non-insulin-dependent diabetes.","volume":"2","author":"Perlmuter","year":"1998","journal-title":"J Diabetes Complications"},{"key":"2020071612265931800_R21","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S0960-894X(03)00089-1","article-title":"The newly synthesized linoleic acid derivative FR236924 induces a long-lasting facilitation of hippocampal neurotransmission by targeting nicotinic acetylcholine receptors.","volume":"13","author":"Tanaka","year":"2003","journal-title":"Bioorg Med Chem Lett"},{"key":"2020071612265931800_R22","first-page":"208","volume":"267","author":"Shang","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071612265931800_R23","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1152\/jn.1998.80.1.452","article-title":"Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1.","volume":"80","author":"Klann","year":"1998","journal-title":"J Neurophysiol"},{"key":"2020071612265931800_R24","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1523\/JNEUROSCI.22-03-00674.2002","article-title":"Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C.","volume":"22","author":"Knapp","year":"2002","journal-title":"J Neurosci"},{"key":"2020071612265931800_R25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jnr.10371","article-title":"Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory?","volume":"70","author":"Knapp","year":"2002","journal-title":"J Neurosci Res"},{"key":"2020071612265931800_R26","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.neuint.2006.03.006","article-title":"NMDA and non-NMDA receptors stimulation causes differential oxidative stress in rat cortical slices.","volume":"49","author":"Sanganahalli","year":"2006","journal-title":"Neurochem Int"},{"key":"2020071612265931800_R27","doi-asserted-by":"crossref","first-page":"8106","DOI":"10.1523\/JNEUROSCI.1362-04.2004","article-title":"Vulnerability of central neurons to secondary insults after in vitro mechanical stretch.","volume":"24","author":"Arundine","year":"2004","journal-title":"J Neurosci"},{"key":"2020071612265931800_R28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10517-005-0404-1","article-title":"Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA.","volume":"140","author":"Boldyrec","year":"2005","journal-title":"Bull Exp Biol Med"},{"key":"2020071612265931800_R29","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.peptides.2005.10.006","article-title":"Effects of leptin on memory processing.","volume":"27","author":"Farr","year":"2006","journal-title":"Peptides"},{"key":"2020071612265931800_R30","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1037\/0735-7044.118.3.479","article-title":"Intraventricular insulin and leptin reverse place preference conditioned with high-fat diet in rats.","volume":"118","author":"Figlewicz","year":"2004","journal-title":"Behav Neurosci"},{"key":"2020071612265931800_R31","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0306-4522(02)00162-8","article-title":"Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents.","volume":"113","author":"Li","year":"2002","journal-title":"Neuroscience"},{"key":"2020071612265931800_R32","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.peptides.2004.03.018","article-title":"Orexin-A (hypocretin-1) and leptin enhance LTP in the dentate gyrus of rats in vivo.","volume":"25","author":"Wayner","year":"2004","journal-title":"Peptides"},{"key":"2020071612265931800_R33","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1210\/en.2003-1582","article-title":"Circulating triglycerides impact on orexigenic peptides and neuronal activity in hypothalamus.","volume":"145","author":"Chang","year":"2006","journal-title":"Endocrinology"},{"key":"2020071612265931800_R34","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nn1656","article-title":"Ghrelin controls hippocampal spine synapse density and memory performance.","volume":"9","author":"Diano","year":"2006","journal-title":"Nat Neurosci"},{"key":"2020071612265931800_R35","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0196-9781(03)00160-8","article-title":"Ghrelin-induced feeding is dependent on nitric oxide.","volume":"24","author":"Gaskin","year":"2003","journal-title":"Peptides"},{"key":"2020071612265931800_R36","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/S0196-9781(02)00110-9","article-title":"Effects of orexin-A on memory processing.","volume":"23","author":"Jaeger","year":"2002","journal-title":"Peptides"},{"key":"2020071612265931800_R37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.peptides.2004.12.004","article-title":"Orexin-1-induced feeding is dependent on nitric oxide.","volume":"26","author":"Farr","year":"2005","journal-title":"Peptides"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/149\/5\/2628\/9005021\/endo2628.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/149\/5\/2628\/9005021\/endo2628.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T16:15:27Z","timestamp":1594916127000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/149\/5\/2628\/2455198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,14]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,5,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2007-1722","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1124068.581188","asserted-by":"object"}]},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,14]]}}}