Posts tagged melanocortin
Articles and news from the latest research reports.
Anorexia/bulimia: A bacterial protein implicated
Eating disorders (ED) such as anorexia nervosa, bulimia, and binge eating disorder affect approximately 5-10% of the general population, but the biological mechanisms involved are unknown. Researchers at Inserm Unit 1073, “Nutrition, inflammation and dysfunction of the gut-brain axis” (Inserm/University of Rouen) have demonstrated the involvement of a protein produced by some intestinal bacteria that may be the source of these disorders. Antibodies produced by the body against this protein also react with the main satiety hormone, which is similar in structure. According to the researchers, it may ultimately be possible to correct this mechanism that causes variations in food intake.
These results are published in the journal Translational Psychiatry, in the online issue of 7 October 2014.
Anorexia nervosa, bulimia and binge eating disorder are all eating disorders (ED). If the less well defined and atypical forms are included, ED affect 15-20% of the population, particularly adolescents and young adults. Despite various psychiatric, genetic and neurobiological studies, the molecular mechanism responsible for these disorders remains mysterious. The common characteristic of the different forms of ED is dysregulation of food intake, which is decreased or increased, depending on the situation.
Sergueï Fetissov’s team in Inserm Joint Research Unit 1073, “Nutrition, inflammation and dysfunction of the gut-brain axis” (Inserm/University of Rouen), led by Pierre Déchelotte, studies the relationships between the gut and the brain that might explain this dysregulation.
The mimic of the satiety hormone
In this new study, the researchers have identified a protein that happens to be a mimic of the satiety hormone (melanotropin). This protein (ClpB) is produced by certain bacteria, such as Escherichia coli, which are naturally present in the intestinal flora. Where this protein is present, antibodies are produced against it by the body. These will also bind to the satiety hormone because of its structural homology to ClpB, and thereby modify the satietogenic effect of the hormone. The sensation of satiety is reached (anorexia) or not reached (bulimia or overeating). Moreover, the bacterial protein itself seems to have anorexigenic properties.
Variations in food intake in the presence of the bacterial protein
To obtain these results, the researchers modified the composition of the intestinal flora of mice to study their immunological and behavioural response. Food intake and level of antibodies against melanotropin in the 1st group of mice, which were given mutant E. coli bacteria (not producing ClpB) did not change. In contrast, antibody level and food intake did vary in the 2nd group of animals, which received E. coli producing ClpB protein.
The likely involvement of this bacterial protein in disordered eating behaviour in humans was established by analysing data from 60 patients.
The standardised scale “Eating Disorders Inventory-2” was used to diagnose these patients and evaluate of the severity of their disorders, based on a questionnaire regarding their behaviour and emotions (wish to lose weight, bulimia, maturity fears, etc.). Plasma levels of antibodies to ClpB and melanotropin were higher in these patients. Furthermore, their immunological response determined the development of eating disorders in the direction of anorexia or bulimia.
These data thus confirm the involvement of the bacterial protein in the regulation of appetite, and open up new perspectives for the diagnosis and specific treatment of eating disorders.
Correcting the action of the protein mimicking the satiety hormone
"We are presently working to develop a blood test based on detection of the bacterial protein ClpB. If we are successful in this, we will be able to establish specific and individualised treatments for eating disorders," say Pierre Déchelotte and Sergueï Fetissov, authors of this study.
At the same time, the researchers are using mice to study how to correct the action of the bacterial protein in order to prevent the dysregulation of food intake that it generates. “According to our initial observations, it would indeed be possible to neutralise this bacterial protein using specific antibodies, without affecting the satiety hormone,” they conclude.
Brain Response to Appetizing Food Cues Varies Among Obese People
People who have the most common genetic mutation linked to obesity respond differently to pictures of appetizing foods than overweight or obese people who do not have the genetic mutation, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).
More than one-third of adults are obese. Obesity typically results from a combination of eating too much, getting too little physical activity and genetics. In particular, consumption of appetizing foods that are high in calories can lead to weight gain. Highly palatable foods such as chocolate trigger signals in the brain that give a feeling of pleasure and reward. These cravings can contribute to overeating. Reward signals are processed in specific areas of the brain, where sets of neurons release chemicals such as dopamine. However, very little is known about whether the reward centers of the brain work differently in some people who are overweight or obese.
The most common genetic cause of obesity involves mutations in the melanocortin 4 receptor (MC4R), which occur in about 1 percent of obese people and contribute to weight gain from an early age. The researchers compared three groups of people: eight people who were obese due to a problem in the MC4R gene, 10 people who were overweight or obese without the gene mutation and eight people who were normal weight. They performed functional Magnetic Resonance Imaging (fMRI) scans to look at how the reward centers in the brain were activated by pictures of appetizing food such as chocolate cake compared to bland food such as rice or broccoli and non-food items such as staplers.
“In our study, we found that people with the MC4R mutation responded in the same way as normal weight people, while the overweight people without the gene problem had a lower response,” said lead researcher Agatha van der Klaauw, MD, PhD, of the Wellcome Trust-MRC Institute of Metabolic Science at Addenbrooke’s Hospital in Cambridge, U.K. “In fact, the brain’s reward centers light up when people with the mutation and normal weight people viewed pictures of appetizing foods. But overweight people without the mutation did not have the same level of response.”
The scans revealed that obese people with the MC4R mutation had similar activity in the reward centers of the brain when shown a picture of a dessert like cake or chocolate as normal weight people. The researchers found that, in contrast, the reward centers were underactive in overweight and obese volunteers who did not have the gene mutation. This finding is intriguing as it shows a completely different response in two groups of people of the same age and weight.
“For the first time, we are seeing that the MC4R pathway is involved in the brain’s response to food cues and its underactivity in some overweight people,” van der Klaauw said. “Understanding this pathway may help in developing interventions to limit the overconsumption of highly palatable foods that can lead to weight gain.”
To address the obesity epidemic, the Cambridge team is continuing to study the pathways in the brain that coordinate the need to eat and the reward and pleasure of eating
(Source: endocrine.org)