Anorexia nervosa is a severe and potentially fatal eating disorder, and achieving lasting recovery remains a major challenge. Even after prolonged hospital treatment and weight restoration, around 40 percent of patients are re-admitted within six months. Clinicians also lack reliable tools to identify those at greatest risk of relapse.
Researchers are increasingly investigating how anorexia affects metabolism and the brain’s regulation of hunger. A new study published in Translational Psychiatry highlights the role of the hormone ghrelin and its antagonist, liver-expressed antimicrobial peptide 2 (LEAP2). The findings suggest these biological signals could help predict the risk of relapse.
Hunger Hormones Under the Spotlight
Ghrelin is commonly known as the hunger hormone because its levels rise before meals and stimulate appetite. LEAP2 has the opposite effect, reducing ghrelin’s activity. In a healthy system, the balance between these two hormones helps match appetite with the body’s energy requirements. In anorexia nervosa, however, that balance may become disrupted.
Neuroscientist Virginie Tolle of France’s National Institute of Health and Medical Research and colleagues studied 30 women with anorexia nervosa between the ages of 18 and 60. All participants completed a four-month inpatient refeeding program at a specialized eating disorder center. The researchers measured hormone levels before treatment, after four months, and again six months later.
At hospital admission, patients had approximately 20 percent higher LEAP2 levels than they did after weight restoration. Because LEAP2 counteracts ghrelin, these elevated levels may suppress normal hunger signals. As a result, patients may find it more difficult to respond to internal cues to eat, even when they are medically underweight.
Link Between LEAP2 and Relapse Risk
After four months of treatment, the researchers analyzed the ratio of ghrelin to LEAP2 and compared it with measures of impulse control. They found that the ratio was negatively correlated with impulsivity among patients who later maintained a stable weight. In other words, improved hormonal balance was associated with better self-control and more sustained recovery.
Among patients who later relapsed and lost weight again, LEAP2 levels returned to the elevated values seen before treatment. This pattern suggests that LEAP2 could serve as a biochemical marker for identifying patients at increased risk of returning to dangerous food restriction soon after leaving hospital care.
To investigate the underlying biology further, the researchers also conducted experiments in mice placed on a restricted diet until they had lost approximately one-quarter of their body weight. The animals were then tested using tasks that required them to choose between a small, immediate food reward and a larger, delayed reward, providing a measure of impulsivity.
Mice that had undergone food restriction became more impulsive, showing a greater tendency to choose the smaller, immediate reward. This behavior improved only partially after refeeding. Elevated LEAP2 levels were strongly associated with these persistent impulsive choices, suggesting the hormone may influence food-related decision-making even after weight restoration.
Toward New Tools and Treatments
According to the authors, the findings suggest that prolonged food restriction alters metabolic signals in ways that influence cognition and food-related decision-making. These biological changes may help determine whether patients are able to maintain healthy eating behaviors and body weight after discharge. Hormonal markers could one day help clinicians tailor treatment according to an individual’s risk of relapse.
If the findings are confirmed in larger and more diverse patient populations, a simple blood test measuring LEAP2 and ghrelin could help identify individuals who require more intensive follow-up or earlier intervention. Such a tool would represent a significant advance in a field where pharmacological treatment options remain extremely limited and relapse rates continue to be high.
The research also raises the possibility of developing therapies that target LEAP2 or related biological pathways. By modulating this natural antagonist of ghrelin, future treatments might promote more stable appetite regulation and reduce the compulsive food restriction and hyperactivity frequently observed in anorexia nervosa.
Tolle emphasizes that anorexia nervosa has the highest mortality rate of any psychiatric disorder and currently has no approved, effective medication. She argues that understanding how metabolic hormones influence the brain and decision-making is essential for developing more effective treatments and improved monitoring strategies.
Although the findings are promising, the study has several limitations, including its relatively small sample size and its focus on female inpatients. Experts note that replication in larger, multi-center studies, as well as in adolescents, who account for a substantial proportion of anorexia nervosa cases, will be necessary before LEAP2 can be incorporated into routine clinical practice.
Specialists also caution that no biomarker can replace comprehensive multidisciplinary care, which typically includes nutritional rehabilitation, psychotherapy, medical monitoring, and family support. Instead, biomarkers such as LEAP2 would likely complement these approaches by helping clinicians monitor relapse risk over time and adjust care accordingly.
As research into hormones such as ghrelin and LEAP2 continues, it is reshaping scientists’ understanding of eating disorders by highlighting not only their psychological dimensions but also their underlying biological mechanisms. This perspective could eventually help reduce stigma and pave the way for more precise, personalized treatments for patients and their families.
