Barcelona, Spain: People with anorexia nervosa have unusually high levels of a hormone called LEAP2 in their blood when they are in the acute phase of the disorder, according to research presented today (Thursday) at the Federation of European Neuroscience Societies (FENS) Forum 2026 [1]. Patients with the highest levels of LEAP2 are more likely to relapse following treatment for anorexia nervosa.
The research suggests that levels of this hormone are linked to the ability to control impulses. This could be a factor in avoiding food in anorexia nervosa or, in contrast, in emotional eating in patients with binge eating and purging behaviours.
The researchers have also found that the LEAP2 hormone seems to be linked to blood sugar regulations and an abnormal tolerance to being underfed, which may help explain why patients can restrict their eating for months or years.
Researchers say their discoveries help us understand the link between the physical and mental problems that underlie eating disorders and they could lead to better testing and new ways of treating anorexia nervosa in the future.
The research was presented by Dr Virginie Tolle, a neuroscientist at INSERM (France's Institut de la Santé et de la Recherche Médicale) working at the Institute of Psychiatry and Neuroscience of Paris, France.
She said: "Anorexia nervosa is a complex disorder predominantly affecting young women. It is characterised by self-imposed food restriction, often accompanied by hyperactivity, which together can lead to severe undernutrition and potentially life-threatening consequences. Indeed, anorexia nervosa has the highest mortality rate amongst all psychiatric disorders.
"Despite its severity, there is currently no effective drug to treat this disorder. Existing treatments rely on nutritional rehabilitation and multidisciplinary care; however, recovery can take many months and relapse rates remain high, reaching up to 40%. Over the past decade, we've seen growing evidence that anorexia nervosa is not only a psychiatric condition, but also a disorder with a metabolic cause."
Dr Tolle and her colleagues study anorexia nervosa in humans and in mice, allowing them to link clinical and behavioural observations in patients with studies of the brain and metabolism that can only be conducted in animals.
The research included 30 women aged between 18 and 60 years who were diagnosed with anorexia nervosa and were treated with a four-month refeeding programme in a specialised eating disorders centre (Clinique des Maladies Mentales et de l'Encéphale, Sainte-Anne Hospital, Paris, France). The patients gave blood samples before treatment, after treatment and again six months later. They also completed detailed questionnaires about their behaviour.
In previous research, Dr Tolle had been studying a hormone called ghrelin. Under normal circumstance, this hormone is released by the stomach in response to hunger and signals to the brain that it is time to eat. In people with anorexia nervosa, this process seems to go wrong.
Dr Tolle and her colleagues discovered that patients with anorexia nervosa had 20% higher levels of another hormone called LEAP2 (liver-expressed antimicrobial peptide 2) in their blood when they were first hospitalised for anorexia nervosa, compared to their levels after four months of hospital treatment. The LEAP2 hormone, which is produced by the liver and intestines, works against ghrelin, effectively overriding the body's normal hunger signals. This difference was particularly apparent in patients who relapsed six months after being discharged from hospital.
This finding, if confirmed in a larger number of patients, suggests that testing levels of LEAP2 could predict who is likely to relapse, meaning treatment and care can be tailored to provide the right level of support. Learning more about this molecule and how it relates to anorexia nervosa might also lead to the development of a pharmacological treatment for patients in the future.
The questionnaires revealed that patients who had higher scores of impulse control after four months of hospital treatment (when they re-gained weight) had relatively less of the ghrelin hormone compared to levels of LEAP2 in their blood, especially those patients who were able to maintain their weight gain six months after treatment.
The researchers also studied the levels of ghrelin and LEAP2 in a group of mice. To recreate the nutritional state of anorexia nervosa, a group of young female mice were fed normally, then their food was restricted to 50% for 15 days, before normal feeding was restored. Impulsivity was tested by giving mice the choice between a small food reward that was delivered immediately, or a larger reward that was delivered after a time delay.
Researchers found that the mice were more impulsive when their food was restricted and their impulsivity was only partially restored by refeeding. Higher levels of LEAP2 were also linked to higher impulsivity when the mice were being refed.
Taken together, these results suggest that LEAP2 could play a role in the connection between the digestive system and the brain and how this goes wrong in anorexia nervosa.
Dr Tolle said: "Our findings suggest that metabolic signals that normally regulate hunger adapt differently in pathological eating such as anorexia nervosa. These signals also influence the brain and decision-making processes.
"What we have learned about LEAP2 suggest it is a potential target for much-needed new therapeutic strategies. In addition, our research identifies LEAP2 as a biomarker of relapse, suggesting it could be possible to test and monitor patients and adapt treatment as needed."
Dr Tolle and her team have also found that mice with restricted food who are treated with the LEAP2 hormone have difficulty regulating their blood sugar.
Dr Tolle explained: "Recent research has shown that there is a genetic link between anorexia nervosa and metabolic traits such as blood glucose and insulin resistance. This is important because it redefines anorexia nervosa as being a disorder with both metabolic and psychiatric origins.
"Our most recent findings suggest that in anorexia nervosa there could be a 'metabolic tolerance' to being underfed and in some patients that may predict their tolerance to being able to diet for many months or even years. If LEAP2 is a biomarker of this tolerance to undernutrition, then it could be used to predict which patients may be at higher risk of the most serious, long-term illness."
The researchers plan to study anorexia nervosa in a larger group of patients and to use new techniques to measure how ghrelin and LEAP2 modify the activity of cells in the brain, working towards more effective treatments.
Professor Christina Dalla from the National and Kapodistrian University of Athens, Greece, is chair of the FENS Forum communication committee and was not involved in the research. she said: "Anorexia nervosa is a highly complex disorder influenced by many biological, psychological, and environmental factors. This condition cannot be fully captured in animal models. However, by combining data on patients with mouse studies, the researchers have been able to learn more about the biological mechanisms underlying anorexia nervosa.
"This research helps explain how changes in metabolism and nutrition may affect the brain's reward system, which could influence eating behaviour. By studying the complex factors that contribute to anorexia nervosa, we will gain better understanding of this disorder and ultimately find new personalised treatment strategies for patients."
