Changes in agouti-related protein and symptom improvement in drug-naïve Chinese female patients with anorexia nervosa: a 6-month real-world longitudinal study

Agouti-related protein (AgRP) is an orexigenic neuropeptide that also plays a role in stereotypic behaviors and cognitive impairments. This study examined whether plasma AgRP levels are associated with eating disorder symptom severity and longitudinal symptom changes in anorexia nervosa (AN). This study included 53 drug-naïve patients diagnosed with AN, comprising 41 with the restricting subtype (AN-R) and 12 with the binge/purging subtype (AN-BP), along with 43 healthy controls (HC). At baseline, all participants underwent fasting blood sampling for plasma AgRP measurement and completed the Eating Disorder Examination Questionnaire, Version 6 (EDE-Q). During the 6-month follow-up, patients received routine clinical treatment, and 32 patients underwent repeat AgRP measurement and clinical reassessment. Baseline variables were compared using Mann-Whitney U tests for two-group comparisons or Kruskal-Wallis tests for three-group comparisons, with Bonferroni correction applied for post-hoc analyses. Changes between baseline and follow-up were assessed using the Wilcoxon signed-rank test. Associations between AgRP levels and clinical measures were examined using Spearman correlation and linear regression analyses, with Bonferroni correction applied for multiple comparisons. The study found elevated plasma AgRP concentrations in patients with AN, with post hoc analyses indicating higher levels in AN-R compared with HC, while no significant differences were observed between AN-R and AN-BP or between AN-BP and HC. During the 6-month follow-up, AgRP concentrations in patients with AN declined and approached levels observed in HC. Among the 32 patients with AN who completed follow-up, baseline AgRP levels were negatively correlated with follow-up EDE-Q total scores. Body mass index (BMI) was negatively correlated with AgRP levels in all participants. Partial correlation, controlling for baseline BMI, showed that changes in AgRP were positively correlated with improvements in EDE-Q total scores. This association remained significant in regression analysis after adjusting for BMI. AgRP levels were elevated in patients with AN at baseline and decreased to levels comparable with HC during treatment, with the magnitude of reduction associated with improvements in EDE-Q total scores. These findings suggest that dynamic changes in AgRP may serve as a biological correlate of the metabolic and clinical recovery process in AN. People with anorexia nervosa (AN) often restrict food, leading to low weight, due to concerns about weight and body image. Research suggests that their difficulty in maintaining a healthy weight may also involve changes in how the body regulates energy and metabolism. A key system involved in hunger and energy balance is the Agouti-related protein (AgRP) system in the brain, which helps regulate appetite. To explore the relationship between AgRP and symptom changes in AN, this study measured plasma AgRP levels in 53 patients with AN and 43 healthy controls (HC). This study found that, compared with HC, patients with AN had higher AgRP levels, particularly those with the restricting subtype, while no significant difference was observed between AN-R and AN-BP. After six months of treatment, AgRP levels in AN decreased to levels similar to HC, reflecting normalization alongside clinical improvement. Higher starting AgRP levels were linked to fewer eating disorder symptoms later, and a greater reduction in AgRP was linked to more symptom improvement. These findings suggest that reductions in AgRP occur alongside recovery and may reflect improvements in nutritional and clinical status. Therefore, AgRP may serve as a potential biological indicator of disease improvement, and longitudinal tracking of AgRP may provide insights into the recovery process in AN.