title: High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1β, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism.
abstract: High-fat diet (HFD)-induced obesity is reaching worldwide proportions. In addition to causing obesity, HFDs also induce a variety of health disorders, which includes cognitive decline. Hippocampal function may be particularly vulnerable to the negative consequences of HFD, and it is suspected that 'primed' neuroinflammatory processes may mediate this response. To examine the link between diet, hippocampal function and neuroinflammation, male Wistar rats were fed a medium or HFD. Hippocampal memory function was measured using contextual pre-exposure fear conditioning (CPE-FC). Rats fed a HFD demonstrated impaired memory, an effect that was augmented with longer duration of HFD consumption. HFD-induced memory impairments were linked to potentiated levels of interleukin-1 beta (IL-1β) protein in the hippocampus 2h after the foot-shock that occurs during CPE-FC. Central IL-1 receptor antagonism, with intracisterna magna (ICM) administration of hIL-1RA prior to the foot-shock prevented the diet-induced memory disruption, suggesting a critical role for IL-1β in this phenomenon. Additionally, obese animals whose diet regimen was reversed from HFD back to standard chow recovered memory function and did not demonstrate a foot-shock-induced hippocampal IL-1β increase. Interestingly, dietary reversal neutralized the negative impact of HFD on memory and IL-1β, yet animals maintained physiological evidence of obesity (increased body mass and serum leptin), indicating that dietary components, not body mass, may mediate the negative effects on memory.
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: julia.sobesky@colorado.edu.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Sobesky
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Barrientos
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Henning S
authors.initials: HS
authors.lastname: De May
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Thompson
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weber
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D059305:Diet, High-Fat; D005239:Fear; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1
keywords: Dietary reversal; Fear conditioning; High-fat diet; Hippocampus; Interleukin-1β; Memory; hIL-1RA