We are what we eat, so the saying goes. Not only does a high-calorie diet impact physical health, it also affects the state of mind. That’s been known for some time. But new research published in Neuroscience provides evidence, in rats, that mental health may be impacted by diet surprisingly quickly.

A growing body of research shows that obesity can increase the risk of stress and anxiety. But the new study by researchers in Brazil published in IBRO’s flagship journal provides evidence that a diet that includes a large amount of calorie-dense food can affect mental health in as little as two weeks.

“Obesity is among the most prevalent chronic diseases in the world,” says Dr Arthur Rocha-Gomes, a postdoctoral researcher at University of São Paulo, Brazil, co-first author of the study. At the same time, anxiety is one of the most prevalent mental health conditions worldwide and studies have made a clear connection between obesity and anxiety. It means that trying to understand more about the obesity-anxiety link is a priority. While many studies have investigated the long-term effects of a high-sugar, high-fat diet on anxiety, this research looked at what happens in the short term.

> Dr. Arthur Rocha-Gomes

Rocha-Gomes and his fellow researchers fed male Wistar rats two different high calorie diets, known as ‘cafeteria diets’, for two weeks. These two high calorie diets included slightly different combinations of high sugar, high fat and ultra-processed foods such as milk chocolate, mozzarella cheese, cookies and instant noodles. A control group of rats was just fed a standardized rat food.

Three classical tests were used to measure anxiety levels in the rats. The light-dark box, which consists of two chambers – one with black colored walls and red light and the other with white walls and white light. The elevated plus maze, which consists of four elevated sections at right angles to one another, with two sections having walls and two being open. Finally, the open field arena consisting of a square walled area without a roof. In the wild, rats will avoid bright, open areas that would make them more visible to predators and lab-based research has shown this threat avoidance is elevated by anxiety.

In this study, rats fed the cafeteria diets tended to spend more time in the dark chamber of the light-dark box compared with the control group. In the elevated plus maze, high calorie diet rats entered the closed arms more and into the open arms less than the control group. In the open maze test, the high calorie diet rats spent less time in the centre and more time at the periphery compared to the control group. Taken together, these differences indicated the rats fed the high calorie diets were displaying more threat avoidance behaviours, indicating higher levels of anxiety.

The researchers were also interested in investigating the mechanism behind these rapid changes in anxiety. Existing, longer term, research has already established a link between obesity, inflammation and anxiety. “When a person or rat accumulates fat mass, this tissue can express more cytokines,” says Rocha-Gomes. “So there is systemic inflammation. The cytokines can pass through the blood-brain barrier to reach the brain and if this inflammation reaches a key structure related to anxiety response, like the amygdala, the rat or the person could develop an anxiety response.” Rocha-Gomes and his fellow researchers wanted to find out whether these changes could take place in two weeks, so they measured levels of two cytokines responsible for inflammation, Tumor Necrosis Factor Alpha (TNF-α) and Interferon-γ (INFγ) in the rats.

Members of the lab where the study was conducted. From left to right: Dr. Tania Regina Riul, Dr. Arthur Rocha-Gomes, Dalila Gomes, Camilla Santiago, Alexandre Alves, Tatiele Pereira. Missing team members: Clarisse Reis, Amanda Escobar and Dr. Eduardo Oliveira.

In just two weeks, the rats fed the cafeteria diets started to produce excessive adipose tissue – they started to gain weight. These rats also had higher levels of Tumor Necrosis Factor Alpha (TNF-α) and Interferon-γ (INFγ) compared to the control group. Higher levels of TNF-α were also found in the amygdalae, a brain structure involved with emotional responses, of the rats fed the cafeteria diets than in the control group. 

“Our study is the first that has shown two different types of cafeteria diets lead to an anxiety response in rats, even over a short period of time,” says Rocha-Gomes. While the ultimate impact of the two cafeteria diets on the two groups of rats was the same in that both had elevated cytokine levels and increased anxiety, their macronutrient intake differed. The rats fed a more varied cafeteria diet, which gave them more choice in what they consumed, ate more carbohydrates than rats fed a less varied cafeteria diet. In their Neuroscience study, the researchers note that the varied cafeteria diet is closer to the types of food consumed in an unhealthy human diet.

Rocha-Gomes says caution is needed when seeking to apply what was found in the rats to humans:

“This was a preclinical study, so it’s difficult to estimate the direct impacts on society. Some studies with humans show that short-term hypercaloric diets are associated with lower mood and higher stress levels without revealing direct relationships yet. However, more studies would be needed to evaluate whether the outcomes shown in our study could be extrapolated to humans.”

Rocha-Gomes acknowledges the limitations of the research, co-first authored by Clarisse Giovana Maciel Reis, a researcher at Federal University of Vales do Jequitinhonha e Mucuri, Brazil. “The main limitation was the use of only male animals. So we were unable to assess if short term cafeteria diets also affect females. We also only evaluated the effect of a cafeteria diet at 14 days. We don’t know if this response would be observed with a shorter or longer period. In future studies, we will try to evaluate the effect of this diet over three or four weeks.” While the connection between obesity, cytokines and anxiety is known, more research is needed to understand all the mechanisms by which a high calorie diet leads to changes in mental health, including whether microglia, cells in the brain and spinal cord that are the main form of immune response in the central nervous system, play a role in the obesity-inflammation-anxiety mechanism.

In the future, says Rocha-Gomes, food policy needs to change to discourage high consumption of foods which contain high levels of fat and sugar, even in the short term. He says the harmful effects of these types of food need to be clearer to consumers and for campaigns to take place on social media about hypercaloric diets.

This was Rocha-Gomes’s first study published in Neuroscience and he says it was a positive experience. “We had a good experience during the review process. The comments made by the reviewers helped to improve our paper substantially.” He has a tip for anyone planning to publish their research in Neuroscience. “The format recommended by Neuroscience for figures is different from other journals. It’s imperative for authors to check this before submitting their work.”

This article was written by Dr. Andy Ridgway.

About Neuroscience

Established in 1976, Neuroscience is the flagship journal of IBRO. The journal features papers describing the results of original research on any aspect of the scientific study of the nervous system. Papers of any length are considered for publication provided that they report significant, new, and carefully confirmed findings with full experimental details. Together with IBRO Neuroscience Reports, IBRO’s open access journal, Neuroscience plays a crucial role in supporting the organization’s global neuroscience activities, as ​​proceeds from both journals support more than 90% of IBRO’s initiatives.

Learn more about Neuroscience.