title: Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1.
abstract: There is growing evidence that over consumption of high-fat foods and insulin resistance may alter hippocampal-dependent cognitive function. To study the individual contributions of diet and peripheral insulin resistance to learning and memory, we used a transgenic mouse line that overexpresses ecto-nucleotide pyrophosphatase phosphodiesterase-1 in adipocytes, which inhibits the insulin receptor. Here, we demonstrate that a model of peripheral insulin resistance exacerbates high-fat diet induced deficits in performance on the Morris Water Maze task. This finding was then reviewed in the context of the greater literature to explore potential mechanisms including triglyceride storage, adiponectin, lipid composition, insulin signaling, oxidative stress, and hippocampal signaling. Together, these findings further our understanding of the complex relationship among peripheral insulin resistance, diet and memory.
authors.affiliation: Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States. Electronic address: jakasper@utmb.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Kasper
authors.affiliation: Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: A J
authors.initials: AJ
authors.lastname: Milton
authors.affiliation: Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: A E
authors.initials: AE
authors.lastname: Smith
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: F
authors.initials: F
authors.lastname: Laezza
authors.affiliation: Mitchell Center for Neurodegenerative Disease, Department of Neurology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: G
authors.initials: G
authors.lastname: Taglialatela
authors.affiliation: Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: J D
authors.initials: JD
authors.lastname: Hommel
authors.affiliation: Division of Internal Medicine, Department of Endocrinology, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: N
authors.initials: N
authors.lastname: Abate
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases