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Anitbodies

Antibodies linked to ghrelin and appetite regulation

Immunoglobulins have different properties in obese patients
Pierre Déchelotte

Certain antibodies have a greater affinity for ghrelin in obese patients leading to extended appetite stimulation, according to the results of a study published in the journal Nature Communications.

It is well documented that many morbidly obese people continue to consume too much food (hyperphagia) compared to their reserves and their needs. However, ghrelin is most frequently found at a normal or even lower level in these patients.

Now, a team from Inserm/University of Rouen, France, in collaboration with Professor Akio Inui's team at the University of Kagoshima, Japan, has revealed the molecular mechanism of this paradoxical hyperphagia.

The study conducted by Sergueï Fetissov and the team from joint research unit 1073 ‘Nutrition, inflammation and dysfunction of the gut-brain axis’, directed by Pierre Déchelotte, highlighted the presence of specific antibodies, or immunoglobulins, in the blood of obese patients, antibodies that recognise ghrelin and regulate appetite.

By binding to ghrelin, the immunoglobulins protect the hunger hormone from being broken down rapidly in the bloodstream. The ghrelin can then act on the brain for longer and stimulate appetite.

"The immunoglobulins have different properties in obese patients", said Sergueï Fetissov, researcher in the Inserm unit in Rouen and main author of the study. "They are more strongly 'attracted' to ghrelin than in subjects of normal weight or in anorexic patients. It is this difference in 'affinity' that enables the immunoglobulins to transport more ghrelin to the brain and boost its stimulating action on food intake."

The research team has confirmed this mechanism by experiments in rodents. When ghrelin was administered in combination with immunoglobulins extracted from the blood of obese patients, or with immunoglobulins derived from genetically-obese mice, they stimulated food intake more strongly.

Conversely, when ghrelin only was given, or combined with immunoglobulins from non-obese people or mice, the rodents were better able to regulate their appetite by restricting food intake.

"Our discover open a new opportunity to design treatments acting on the basis of this mechanism to reduce hyperphagia observed in cases of obesity", said Déchelotte, Director of the joint Inserm/University of Rouen unit.

"Our results could also be used to study the opposite phenomenon, loss of appetite, such as observed in cases of anorexia.

This study extends other work by the research team, published in 2011, on the role of immunoglobulins interfering with different hormones acting on appetite, satiety or anxiety in cases of anorexia, bulimia or depression, and on the probable involvement of intestinal flora (microbiotic) in these interactions.

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