title: Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice.
abstract: Although the increasing rate of obesity has stimulated interest in the effects of diet composition on peripheral systems, comparatively little work has been done to examine effects upon the brain. A diet high in fat is one of many factors that can promote obesity, and previous research has shown that such a diet can produce learning and memory impairment in rodents. In the present study, C57BL/6 mice were placed on either a high-fat (45% kcal fat) or regular (5% kcal fat) diet, and examined at different points during the subsequent year. The high-fat diet led to increased weight gain, significant impairment in glucoregulation, and altered insulin-mediated signaling within the hippocampus, an area of the brain believed to be important for the acquisition of memory. Following ten months on either diet, synaptic function in ex vivo hippocampal slices was examined, and neither stimulus-response curves nor electrically induced long-term potentiation were found to be different. As well, performance in the Morris water maze, a hippocampal-dependent test of spatial memory, was not influenced by diet. However, mice consuming a high-fat diet failed to perform an operant bar-pressing task, indicating a significant impairment to procedural learning and consolidation processes. Despite causing broad peripheral changes in C57BL/6 mice, consuming a large proportion of calories from saturated fat had only a limited effect upon learning and memory, which suggests that certain aspects of brain function are selectively vulnerable to the influences of diet.
authors.affiliation: Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, 1200 Montreal Road, Building M-54, Ottawa, Ont., Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Mielke
authors.forename: Katarina
authors.initials: K
authors.lastname: Nicolitch
authors.forename: Vanessa
authors.initials: V
authors.lastname: Avellaneda
authors.forename: Karen
authors.initials: K
authors.lastname: Earlam
authors.forename: Tarun
authors.initials: T
authors.lastname: Ahuja
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Mealing
authors.forename: Claude
authors.initials: C
authors.lastname: Messier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology*; D004041:Dietary Fats / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006624:Hippocampus / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D004041:Dietary Fats; D007328:Insulin; D005947:Glucose