ReviewEffects of high-fat diet exposure on learning & memory
Introduction
Consumption of a high-fat (HF) diet has long been known to increase one's risk for a number of medical conditions including obesity, diabetes, and the metabolic syndrome. Further evidence in humans and rodents suggests that these same conditions are associated with an increased risk of Alzheimer's disease and other forms of cognitive impairment [1], [2], [3]. Given the expanding global burden of high fat diet consumption and obesity, and an emerging crisis of dementia due to a rapidly aging population, understanding the effects of high-fat diet consumption on cognition, gaining insights into potential underlying mechanisms, and developing effective treatment strategies are of critical importance. Here, we will review the methods that are most commonly used to assess learning and memory in rodent models, and we will then summarize findings from behavioral studies of the effects of HF diet before discussing potential underlying mechanisms. Finally, we will briefly examine emerging data suggesting that maternal high fat diet consumption may have effects on the offspring's metabolism, neurodevelopment, and cognition.
Section snippets
Behavioral phenotypes
First, it should be noted that in rodent studies of the effects of HF diet on learning and memory, there is tremendous diversity in the choice of animal strain, age, diet, length of exposure, and method of assessing behavioral outcomes with very few studies using multiple tests of cognition. In order to avoid over-generalization of findings from various studies, we have organized this review by behavioral test. The tests included here are not intended to be exhaustive, but they include those
Insulin, leptin & glucose regulation
As HF diet intake has been found to result in impaired performance across a number of tests of cognition, several potential mechanisms have been proposed. Directly connecting the effects of a HF diet on energy metabolism to its effects on cognition is a large body of evidence suggesting that the insulin receptor is highly expressed in the hippocampus and cortex, that synaptic insulin signaling is critical for learning and memory, and that peripheral insulin insensitivity can have dramatic
Developmental programming by maternal diet
A growing body of evidence is suggesting that maternal diet during gestation and the postnatal period can have a profound and long lasting effect on the brain, behavior, and metabolism of the offspring [125]. For example, maternal HF diet consumption has been found to result in increased body weight [126], [127] and adiposity [127], [128] of offspring during the early perinatal period. Additionally, maternal HF diet consumption has been shown to increase food intake and body weight [127] and
Conclusions, implications & future directions
While use of varying diets, ages, and behavioral tests make comparison between individual experiments difficult, the overwhelming majority of studies support the conclusion that HF diet exposure can have a dramatic and long lasting impact on hippocampal dependent learning and memory. While there are clear suggestions that other brain regions (especially the prefrontal cortex) are likely to be affected, results from behavioral tests that assess more distributed neural networks or non-hippocampal
Disclosures
The authors have no conflicts of interest to declare.
Acknowledgments
This manuscript is based on work presented at the 2014 Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), July 29–August 2, 2014. We thank SSIB for the New Investigator Travel Award to Z.A.C. to attend the meeting and present his work. We also thank Dr. Timothy Moran for his mentorship and feedback on this review.
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