Evidence of behavioral, biological similarities between compulsive overeating and addiction

October 17, 2019

Science Daily/Boston University School of Medicine

Does yo-yo dieting drive compulsive eating? There may be a connection.

According to Boston University School of Medicine (BUSM) researchers the chronic cyclic pattern of overeating followed by undereating, reduces the brain's ability to feel reward and may drive compulsive eating. This finding suggests that future research into treatment of compulsive eating behavior should focus on rebalancing the mesolimbic dopamine system -- the part of the brain responsible for feeling reward or pleasure.

An estimated 15 million people compulsively eat in the U.S. It is a common feature of obesity and eating disorders, most notably, binge eating disorder. People often overeat because it is pleasurable in the short term, but then attempt to compensate by dieting, reducing calorie intake and limiting themselves to "safe," less palatable food. However, diets often fail, causing frequent "relapse" to overeating of foods high in fat and sugar (palatable foods).

"We are just now beginning to understand the addictive-like properties of food and how repeated overconsumption of high sugar -- similar to taking drugs -- may affect our brains and cause compulsive behaviors," said corresponding author Pietro Cottone, PhD, associate professor of pharmacology & experimental therapeutics at BUSM and co-director of the Laboratory of Addictive Disorders.

In order to better understand compulsive and uncontrollable eating, Cottone and his team performed a series of experiments on two experimental models: one group received a high sugar chocolate-flavored diet for two days each week and a standard control diet the remaining days of the week (cycled group), while the other group, received the control diet all of the time (control group).

The group that cycled between the palatable food and the less palatable, spontaneously developed compulsive, binge eating on the sweet food and refused to eat regular food. Both groups were then injected with a psychostimulant amphetamine, a drug that releases dopamine and produces reward, and their behavior in a battery of behavioral tests was then observed.

While the control group predictably became very hyperactive after receiving amphetamine, the cycled group did not. Furthermore, in a test of the conditioning properties of amphetamine, the control group was attracted to environments where they previously received amphetamine, whereas the cycled group were not. Finally, when measuring the effects of amphetamine while directly stimulating the brain reward circuit, the control group was responsive to amphetamine, while the cycled group was not.

After investigating the biochemical and molecular properties of the mesolimbic dopamine system of both groups, the researchers determined that the cycled group had less dopamine overall, released less dopamine in response to amphetamine and had dysfunctional dopamine transporters (protein that carries dopamine back into brain cells) due to deficits in their mesolimbic dopamine system.

"We found that the cycled group display similar behavioral and neurobiological changes observed in drug addiction: specifically, a "crash" in the brain reward system," explained Cottone. "This study adds to our understanding of the neurobiology of compulsive eating behavior. Compulsive eating may derive from the reduced ability to feel reward. These findings also provide support to the theory that compulsive eating has similarities to drug addiction."

"Our data suggest that a chronic cyclic pattern of overeating will reduce the brain's ability to feel reward -- feeling satiated. This results in a vicious circle, where diminished reward sensitivity may in turn be driving further compulsive eating," said lead author Catherine (Cassie) Moore, PhD, former graduate student in the Laboratory of Addictive Disorders at BUSM.

The researchers hope these findings spark new avenues of research into compulsive eating that will lead to more effective treatments for obesity and eating disorders.

https://www.sciencedaily.com/releases/2019/10/191017125240.htm

A gut feeling for mental health

February 4, 2019

Science Daily/VIB (the Flanders Institute for Biotechnology)

The first population-level study on the link between gut bacteria and mental health identifies specific gut bacteria linked to depression and provides evidence that a wide range of gut bacteria can produce neuroactive compounds.

In their manuscript entitled 'The neuroactive potential of the human gut microbiota in quality of life and depression' Jeroen Raes and his team studied the relation between gut bacteria and quality of life and depression. The authors combined faecal microbiome data with general practitioner diagnoses of depression from 1,054 individuals enrolled in the Flemish Gut Flora Project. They identified specific groups of microorganisms that positively or negatively correlated with mental health. The authors found that two bacterial genera, Coprococcus and Dialister, were consistently depleted in individuals with depression, regardless of antidepressant treatment. The results were validated in an independent cohort of 1,063 individuals from the Dutch LifeLinesDEEP cohort and in a cohort of clinically depressed patients at the University Hospitals Leuven, Belgium.

Prof Jeroen Raes (VIB-KU Leuven): 'The relationship between gut microbial metabolism and mental health is a controversial topic in microbiome research. The notion that microbial metabolites can interact with our brain -- and thus behaviour and feelings -- is intriguing, but gut microbiome-brain communication has mostly been explored in animal models, with human research lagging behind. In our population-level study we identified several groups of bacteria that co-varied with human depression and quality of life across populations.'

Previously, Prof Raes and his team identified a microbial community constellation or enterotype characterized by low microbial count and biodiversity that was observed to be more prevalent among Crohn's disease patients. In their current study, they surprisingly found a similar community type to be linked to depression and reduced quality of life.

Prof Jeroen Raes (VIB-KU Leuven): 'This finding adds more evidence pointing to the potentially dysbiotic nature of the Bacteroides2 enterotype we identified earlier. Apparently, microbial communities that can be linked to intestinal inflammation and reduced wellbeing share a set of common features.'

The authors also created a computational technique allowing the identification of gut bacteria that could potentially interact with the human nervous system. They studied genomes of more than 500 bacteria isolated from the human gastrointestinal tract in their ability to produce a set of neuroactive compounds, assembling the first catalogue of neuroactivity of gut species. Some bacteria were found to carry a broad range of these functions.

Mireia Valles-Colomer (VIB-KU Leuven): 'Many neuroactive compounds are produced in the human gut. We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows to identify the different bacteria that could play a role in mental health conditions, but also the mechanisms potentially involved in this interaction with the host. For example, we found that the ability of microorganisms to produce DOPAC, a metabolite of the human neurotransmitter dopamine, was associated with better mental quality of life.'

These findings resulted from bioinformatics analyses and will need to be confirmed experimentally, however, they will help direct and accelerate future human microbiome-brain research.

Jeroen Raes and his team are now preparing another sampling round of the Flemish Gut Flora Project that is going to start next spring, five years after the first sampling effort.

https://www.sciencedaily.com/releases/2019/02/190204114617.htm

Gut hormone increases response to food

Ghrelin promotes conditioning to food-related odours

December 12, 2018

Science Daily/McGill University

The holiday season is a hard one for anyone watching their weight. The sights and smells of food are hard to resist. One factor in this hunger response is a hormone found in the stomach that makes us more vulnerable to tasty food smells, encouraging overeating and obesity.

New research on the hormone ghrelin was published on today in Cell Reports on Dec. 4, 2018, led by Dr. Alain Dagher's lab at the Montreal Neurological Institute and Hospital of McGill University.

Previous research by Dr. Dagher's group and others demonstrated that ghrelin encourages eating and the production of dopamine, a neurotransmitter that is important for reward response. In the current study, researchers injected 38 subjects with ghrelin, and exposed them to a variety of odours, both food and non-food based, while showing them neutral images of random objects, so that over time subjects associated the images with the odours.

Using functional magnetic resonance imaging (fMRI), the researchers recorded activity in brain regions known to be involved in reward response from dopamine. They found that activity in these regions was higher in subjects injected with ghrelin, but only when responding to the images associated with food smells. This means that ghrelin is controlling the extent to which the brain associates reward with food odours.

Subjects also rated the pleasantness of the images associated with food odour, and the results showed that ghrelin both reduced the response time and increased the perceived pleasantness of food-associated images, but had no effect on their reaction to images associated with non-food odours.

People struggling with obesity often have abnormal reactivity to the food-related cues that are abundant in our environment, for example fast food advertising. This study shows that ghrelin may be a major factor in their heightened response to food cues. The brain regions identified have been linked to a neural endophenotype that confers vulnerability to obesity, suggesting a genetically-based hypersensitivity to food-associated images and smells.

"Obesity is becoming more common around the world and it's well known to cause health problems such as heart disease and diabetes," says Dr. Dagher. "This study describes the mechanism through which ghrelin makes people more vulnerable to hunger-causing stimuli, and the more we know about this, the easier it will be to develop therapies that counteract this effect."

https://www.sciencedaily.com/releases/2018/12/181212121907.htm

Beer can lift your spirits due to malted barley ingredient

September 27, 2017

Science Daily/Friedrich-Alexander-Universität Erlangen-Nürnberg

Visitors to the Oktoberfest have always known it and now it has been scientifically -- beer can lift your spirits. Scientists examined 13,000 food components to find out whether they stimulate the reward center in the brain and make people feel good. Hordenine which is found in malted barley and beer seems to do the job quite well.

Some foods make us happy. Well, maybe not happy but they make us feel good. That is why we cannot stop eating when we have had enough. Scientists call this hedonic hunger -- the drive to eat for pleasure rather than to satisfy an actual biological need. This feel-good effect is caused by the neurotransmitter dopamine -- tempting foods stimulate the reward centre in the brain where the dopamine D2 receptor is located. Researchers of the Chair of Food Chemistry at FAU investigated whether there are special substances in foods that activate the dopamine D2 receptor in the same way as dopamine.

The team worked with FAU's Computer Chemistry Centre using a virtual screening approach which is often used in pharmaceutical research. This process analyses food components in a computer simulation rather than in the laboratory. Using computer simulations means that all types of known substance can be investigated. In the laboratory, it is only feasible to test a small selection of foodstuff extracts using standard screening techniques.

13,000 molecules, 17 hits

Initially, the scientists set up a database of 13,000 molecules which are present in foodstuffs. Using this database, the objective was to find those molecules that fit the dopamine D2 receptor -- rather like finding the right key for a lock. The system was then used to identify which molecules could interact with the dopamine D2 receptor; these might be present in synthetic substances already known to interact with the receptor, such as medicines for treating Parkinson's and schizophrenia, or which might be candidates for interaction due to the three-dimensional structure of the receptor. In the end, 17 of the original 13,000 options were selected and these were analysed in the laboratory in cooperation with the Division of Medicinal Chemistry at FAU.

Beer -- a surprise finding

The most promising results were obtained for hordenine, a substance present in malted barley and beer. 'It came as a bit of surprise that a substance in beer activates the dopamine D2 receptor, especially as we were not specifically looking at stimulant foodstuffs,' explains Prof. Dr. Monika Pischetsrieder.

Just like dopamine, hordenine stimulates the dopamine D2 receptor, however it uses a different signalling pathway. In contrast with dopamine, hordenine activates the receptor solely through G proteins, potentially leading to a more prolonged effect on the reward centre of the brain. The team is now investigating whether hordenine levels in beer are sufficient to have a significant effect on the reward centre. All things considered, the results indicate that hordenine may well contribute to the mood-boosting effect of beer.

https://www.sciencedaily.com/releases/2017/09/170927152838.htm