Periodic Reporting for period 1 - REBOST (Does excessive junk food consumption change the way the brain reward system processes intrinsic rewards?)
Período documentado: 2020-12-01 hasta 2022-11-30
The prevalence of obesity continues to increase dramatically: 39% of adults are now overweight or obese worldwide (WHO). Excessive consumption of highly palatable sugar and fat laden foods, often in the forms of “junk” or “fast” foods, plays a central role in the development of obesity in humans, due to the food’s hedonic component. This suggests that the reward system plays an important role in the aetiology of obesity.
Feelings of pleasure and motivation are mediated by the brain reward system, which is a collection of brain structures and neural pathways that regulate the response to different rewarding stimuli. Different types of stimuli have attractive and motivational values that induce approach and consummatory behaviour. Food and sexual partners are examples of natural rewards. A dysfunctional reward system is implicated in mental disorders such as depression, addiction, obesity and sexual dysfunctions.
The aim of the REBOST project was to investigate the neurological mechanisms behind the effects of excessive junk food consumption on the reward system by studying the response towards food (primary reward) and sexual behaviour or money (secondary reward), and by distinguishing between the phases of motivation: i) anticipation, ii) approach, and iii) consummatory behaviour, as well as the role of dissatisfaction.
So far, the REBOST project has revealed that long-term junk food exposure does indeed cause long-term alterations to the reward system in the brain. Our preliminary data showed that rats on a junk food diet had lower levels of neural activity in their ventral tegmental area when exposed to either a food or sexual reward. Behaviourally however, the junk food rats only lost interest for a food reward and showed normal levels of sexual behaviour. Two weeks of healthy diet did not reverse these effects.
Feelings of pleasure and motivation are mediated by the brain reward system, which is a collection of brain structures and neural pathways that regulate the response to different rewarding stimuli. Different types of stimuli have attractive and motivational values that induce approach and consummatory behaviour. Food and sexual partners are examples of natural rewards. A dysfunctional reward system is implicated in mental disorders such as depression, addiction, obesity and sexual dysfunctions.
The aim of the REBOST project was to investigate the neurological mechanisms behind the effects of excessive junk food consumption on the reward system by studying the response towards food (primary reward) and sexual behaviour or money (secondary reward), and by distinguishing between the phases of motivation: i) anticipation, ii) approach, and iii) consummatory behaviour, as well as the role of dissatisfaction.
So far, the REBOST project has revealed that long-term junk food exposure does indeed cause long-term alterations to the reward system in the brain. Our preliminary data showed that rats on a junk food diet had lower levels of neural activity in their ventral tegmental area when exposed to either a food or sexual reward. Behaviourally however, the junk food rats only lost interest for a food reward and showed normal levels of sexual behaviour. Two weeks of healthy diet did not reverse these effects.
The REBOST project was divided in three studies, two with animals and one with human participants. In the animal studies, rats were divided in three groups, each with their own six-week diet: healthy control (CTR), high-fat, high sugar (HFHS), or junk food (Cafeteria diet, or CAF). The CAF diet consisted of a choice of the same unhealthy, but tasty products as humans eat (e.g. bacon, muffins, cookies, etc.), mimicking overeating behaviour seen in humans. After the diet, the rats were tested in a reward behaviour test in which they had access to either a food or sexual reward. During the reward behaviour test, fibre photometry was used to measure real-time calcium fluctuations (as indicator of neural activity) in the behaving rats on a millisecond time scale in the ventral tegmental area (VTA, study 1) and the nucleus accumbens (NAc, study 2). In the third study, on the other hand, the effects of junk food consumption on the human brain was investigated. The participants were placed on a diet of either junk food or healthy food for 48h, after which their neural activity during a monetary reward test was assessed using fMRI.
In study 1, long-term exposure to CAF-diet reduced the reward interest towards junk food, shown by a decreased amount of time spent sniffing and eating the junk food reward during the reward behaviour test compared to CTR and HFHS. Interestingly, this reduction in behaviour was accompanied by lower neural activity in the VTA. On the other hand, there was not a clear effect of CAF-diet exposure on interest towards a sexual reward. In fact, all three groups showed similar levels of sexual behaviour (in female rats: paracopulatory behaviour and lordosis responses). However, the neural activity of the VTA was also reduced in CAF-rats during sexual activity. When exposed to dissatisfactory standard chow, CAF-rats also ate significantly less chow compared to CTR- and HFHS-rats. Again, this reduction in reward interest corresponded with lower neural activity in the VTA. Finally, after a period in which all rats were on a healthy food (standard chow) diet, only the behavioural effects towards a CAF reward were partially reversed, while the neural activity in the VTA remained reduced.
Study 2 was a repetition of study 1, but now the effects in the NAc-shell and NAc-core were assessed. Analysis of the data is ongoing, but preliminary results revealed that CAF-diet does not change the neural activity patterns in the NAc-shell and NAc-core compared to CTR-diet during the expectation phase of the reward behaviour test. This could potentially be explained by the existence of D1- and D2- medium spiny neurons in the NAc which play opposite roles upon reward responses. Further data analysis of the other reward phases is needed to understand our preliminary data.
Lastly, analysis of the data from the study 3, the human study, is still ongoing. It has been predicted that junk food exposure will lead to a desensitization of the reward circuit seen during a monetary reward test. Self-reports, however, have already revealed that 48h of junk food intake already increased the negative internal states, such as a reduction of concentration compared to the control group on a healthy food diet.
The preliminary results of the project were presented at the 31st annual meeting of the International Behavioral and Neuroscience Society (IBNS) in Glasgow, June 2022. In addition, we plan to publish the outcomes of study 1 and 2 together in one publication, while the findings of study 3 will be split into 2 publications. All publications will be submitted to high-impact peer-review journals with open access in 2023.
Finally, the various aspects of the project, including the methodology, translational design, and results, have been communicated to a wide range of audiences. The REBOST project featured on national radio and local newspapers, and it was disseminated to students from elementary schools to universities. We also presented the project at the popular science festival "Pint of Science”.
In study 1, long-term exposure to CAF-diet reduced the reward interest towards junk food, shown by a decreased amount of time spent sniffing and eating the junk food reward during the reward behaviour test compared to CTR and HFHS. Interestingly, this reduction in behaviour was accompanied by lower neural activity in the VTA. On the other hand, there was not a clear effect of CAF-diet exposure on interest towards a sexual reward. In fact, all three groups showed similar levels of sexual behaviour (in female rats: paracopulatory behaviour and lordosis responses). However, the neural activity of the VTA was also reduced in CAF-rats during sexual activity. When exposed to dissatisfactory standard chow, CAF-rats also ate significantly less chow compared to CTR- and HFHS-rats. Again, this reduction in reward interest corresponded with lower neural activity in the VTA. Finally, after a period in which all rats were on a healthy food (standard chow) diet, only the behavioural effects towards a CAF reward were partially reversed, while the neural activity in the VTA remained reduced.
Study 2 was a repetition of study 1, but now the effects in the NAc-shell and NAc-core were assessed. Analysis of the data is ongoing, but preliminary results revealed that CAF-diet does not change the neural activity patterns in the NAc-shell and NAc-core compared to CTR-diet during the expectation phase of the reward behaviour test. This could potentially be explained by the existence of D1- and D2- medium spiny neurons in the NAc which play opposite roles upon reward responses. Further data analysis of the other reward phases is needed to understand our preliminary data.
Lastly, analysis of the data from the study 3, the human study, is still ongoing. It has been predicted that junk food exposure will lead to a desensitization of the reward circuit seen during a monetary reward test. Self-reports, however, have already revealed that 48h of junk food intake already increased the negative internal states, such as a reduction of concentration compared to the control group on a healthy food diet.
The preliminary results of the project were presented at the 31st annual meeting of the International Behavioral and Neuroscience Society (IBNS) in Glasgow, June 2022. In addition, we plan to publish the outcomes of study 1 and 2 together in one publication, while the findings of study 3 will be split into 2 publications. All publications will be submitted to high-impact peer-review journals with open access in 2023.
Finally, the various aspects of the project, including the methodology, translational design, and results, have been communicated to a wide range of audiences. The REBOST project featured on national radio and local newspapers, and it was disseminated to students from elementary schools to universities. We also presented the project at the popular science festival "Pint of Science”.
This REBOST project has contributed with new findings linking excessive junk food consumption with alterations on the total brain reward system, both altering the responses upon both intrinsic and extrinsic rewards. The outcomes of this project will not only advance our knowledge on the biological mechanisms of why “junk” or “fast” food is highly consumed by our society beyond cultural and monetary factors, but also reveals the vulnerability of the total reward system. This could contribute to explain the underlying mechanisms of the development of obesity and mental disorders comorbidity with obesity. Ultimately, the results of this project will be beneficial for human health, as it will open up new strategies for biomedical research and therapeutic applications, both for obesity and addiction.