Western Diet Impairs Memory in Rats. Can It Do So in Humans?

• A study on rats published in Brain Behavior and Immunity found that raising them from an early age on Western-style meals resulted in impaired memory function.
• These impairments were dependent on the brain’s hippocampus region and persisted after rats returned to consuming healthy diets.
• The memory impairment was caused by dysregulated acetylcholine signaling.

We all know that eating certain foods can temporarily make us feel bad and unwell. However, more and more studies indicate that following certain dietary patterns might have longer-lasting adverse effects (Hedrih, 2024; Zhang et al., 2024). One such pattern attracting more and more research attention is the so-called Western diet.

The Western diet

The Western diet is broadly defined as a diet high in processed foods, saturated fats, and simple sugars (Hayes et al., 2024). This diet includes many food items rich in both fats and sugars, such as donuts, chocolates, cakes, cookies, milkshakes, and many types of fast food. Studies show that consuming such foods over prolonged periods can contribute to the dysregulation of our food intake control mechanisms, leading to frequent overeating and resulting in overweight and obesity (Hedrih, 2024).

 

Consuming highly processed foods over prolonged periods can contribute to the dysregulation of our food intake control mechanisms.

 

This likely happens because our brains contain separate neural pathways that create rewarding experiences when consuming fats and when consuming sugar. A study on mice identified these pathways and found that because they are separate from each other, their simultaneous activation leads to greater rewarding experiences than the activation of just one of them (McDougle et al., 2024) (see Figure 1). In other words, foods rich in sugars and fats are needed to activate both pathways simultaneously. While humans are different from mice, these particular neural pathways are probably organized in a similar fashion in humans as well.

 

Figure 1. Separate neural pathways create greater rewarding experiences

 

Such foods are rarely found in nature but are abundant in industrial, highly processed foods (Monteiro et al., 2019). Many researchers believe that the widespread consumption of such foods is at least partly behind the obesity pandemic that has developed in large parts of the world in the past decades (Wong et al., 2022).

 

Many researchers believe that the widespread consumption of [industrial, highly processed foods] is at least partially behind the obesity pandemic.

 

Western diet and cognitive dysfunction

Studies on rats also link Western diet consumption with cognitive dysfunction. This is especially true when rats consume Western diets as juveniles (Hsu et al., 2015). One region of the brain that seems particularly vulnerable to the effects of diet during early life is the hippocampus (Hayes et al., 2024).

The hippocampus is a small, curved structure located within the brain’s temporal lobe. Its primary functions include forming and consolidating new memories, spatial navigation, and emotional regulation.

The current study

Study author Anna M.R. Hayes and her colleagues wanted to explore how consuming a Western diet in early life impairs memory function in the short and long term. In their study, they fed cafeteria-style “junk food” to young rats and examined the outcomes.

The study was conducted on male Sprague Dawley rats housed in the animal vivarium at the University of Southern California. They started their assigned experimental diets on their 26th day of life.

The study procedure

The rats were housed individually in hanging wire cages, allowing the study authors to easily collect spilled food and accurately determine how much the rats ate.

Rats were divided into two groups. Researchers prepared a junk food cafeteria-style diet consisting of 20% kcal from protein, 35% from carbohydrates, and 45% from fat. This diet represented the Western diet and was given to one group of rats. The other group of rats ate healthy rat food.

Both groups of rats had free access to their assigned food and water. The first cohort of Western diet rats ate this diet for 60 days, but the study authors shortened it to 30 days for later cohorts. After this period, the study authors started giving healthy food to these rats as well.

These researchers conducted a series of behavioral and metabolic tests on the rats and analyzed their tissues in the end.

Rats fed a Western diet ate 15% more calories during the study period. They also showed deficiencies in contextual episodic memory, which depends on the function of the brain’s hippocampus region. The lower performance of Western diet-raised rats in tasks assessing contextual episodic memory persisted even after the study authors started feeding these rats healthy food (see Figure 2).

 

Figure 2. Procedure (Hayes et al., 2024)

 

Rats fed a Western diet ate 15% more calories during the study period. They also showed deficiencies in contextual episodic memory compared to rats raised on a healthy diet.

 

Other types of memory were not affected. There were also no differences in anxiety markers or how much the rats moved around between the two groups. Rats raised on Western diets also tended to have altered gut microbiome composition, which was reversed after they started eating healthy.

 

Rats raised on a Western diet also tended to have altered gut microbiome composition, which was reversed after they started eating healthy.

 

Memory impairments were caused by reduced acetylcholine signaling in the hippocampus

Memory functions in the hippocampus depend on the neurotransmitter acetylcholine. Study authors found that rats fed a Western diet had lower levels of acetylcholine in the hippocampus. Their cholinergic tone, i.e., the regular, ongoing activity level of acetylcholine in the hippocampus, was lower.

Further analysis revealed that the Western diet disrupted this acetylcholine-based activity, leading to impairments of memory functions that depend on it. Researchers were able to reverse these memory impairments by administering acetylcholine receptor agonists, i.e., substances that mimic the action of acetylcholine. This confirmed that the memory impairments observed due to the Western diet were caused by reduced acetylcholine signaling (see Figure 3).

 

Figure 3. Memory impairments and acetylcholine signaling

 

Conclusion

Overall, the study demonstrated a functional connection between eating a Western diet in early life and long-lasting dysregulation of acetylcholine signaling in the hippocampus, which results in memory impairments.

While these findings were obtained on rats, it is likely that results would not be too dissimilar in humans. Therefore, they help us better understand the biochemical mechanisms linking diet and cognitive health. These and similar findings could potentially help develop programs to better protect human cognitive health.

The paper “Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling” was authored by Anna M.R. Hayes, Logan Tierno Lauer, Alicia E. Kao, Shan Sun, Molly E. Klug, Linda Tsan, Jessica J. Rea, Keshav S. Subramanian, Cindy Gu, Natalie Tanios, Arun Ahuja, Kristen N. Donohue, Léa Décarie-Spain, Anthony A. Fodor, and Scott E. Kanoski.

See other findings on how the Western diet impairs hippocampal functioning in humans in CNP’s Diet-Mental Health Break here.

References

Hayes, A. M. R., Lauer, L. T., Kao, A. E., Sun, S., Klug, M. E., Tsan, L., Rea, J. J., Subramanian, K. S., Gu, C., Tanios, N., Ahuja, A., Donohue, K. N., Décarie-Spain, L., Fodor, A. A., & Kanoski, S. E. (2024). Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling. Brain, Behavior, and Immunity, 118, 408–422. https://doi.org/10.1016/j.bbi.2024.03.015

Hedrih, V. (2024, February 19). Consuming Fat and Sugar (At The Same Time) Promotes Overeating, Study Finds. CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/16563-2/

Hsu, T. M., Konanur, V. R., Taing, L., Usui, R., Kayser, B. D., Goran, M. I., & Kanoski, S. E. (2015). Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats. Hippocampus, 25(2), 227–239. https://doi.org/10.1002/hipo.22368

McDougle, M., de Araujo, A., Singh, A., Yang, M., Braga, I., Paille, V., Mendez-Hernandez, R., Vergara, M., Woodie, L. N., Gour, A., Sharma, A., Urs, N., Warren, B., & de Lartigue, G. (2024). Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metabolism. https://doi.org/10.1016/j.cmet.2023.12.014

Monteiro, C. A., Cannon, G., Levy, R. B., Moubarac, J. C., Louzada, M. L. C., Rauber, F., Khandpur, N., Cediel, G., Neri, D., Martinez-Steele, E., Baraldi, L. G., & Jaime, P. C. (2019). Ultra-processed foods: What they are and how to identify them. Public Health Nutrition, 22(5), 936–941. https://doi.org/10.1017/S1368980018003762

Wong, M. C., Mccarthy, C., Fearnbach, N., Yang, S., Shepherd, J., & Heymsfield, S. B. (2022). Emergence of the obesity epidemic: 6-decade visualization with humanoid avatars. The American Journal of Clinical Nutrition, 115(4), 1189–1193. https://doi.org/10.1093/AJCN/NQAC005

Zhang, L., Sun, H., Liu, Z., Yang, J., & Liu, Y. (2024). Association between dietary sugar intake and depression in US adults: A cross-sectional study using data from the National Health and Nutrition Examination Survey 2011–2018. BMC Psychiatry, 24(110), 1–10. https://doi.org/10.1186/s12888-024-05531-7