2026 ECNP Congress

PS04-4064

Metabolomic signatures of inflammation and energy metabolism across the body mass index spectrum in adolescence: from anorexia nervosa to obesity

Alexandra Vlaic — L. Junquera, N. Martínez-Micaelo, V. Sanchez-Gistau, N. Plana, S. Fernández, A. Rodríguez-Urrutia, S. Samino, C. Girbau, E. Ortigosa, C. Marimon, R. Collell, P. Sol Ventura, Z. Bosch, N. Sanz, A. Bonada, A. Sabaté-Rotés, D. Yeste, A. Feliu, N. Amigó, J.M. Siurana · Vall d’Hebron University Hospital, Mental Health, Barcelona, Spain

2026 ECNP Congress

Background: Extremes of nutritional status during adolescence, including anorexia nervosa (AN) and obesity, are associated with neurobiological and metabolic alterations relevant for psychiatric outcomes[1]. Adolescence represents a period of high anabolic demand and increased sensitivity to psychosocial stress, during which, interactions between metabolic regulation, immune signalling, and brain function may be particularly salient [2]. Metabolomic profiling offers a systems-level approach to characterising these interactions. Prior studies have identified metabolic alterations in anorexia nervosa using this approach[3]. Circulating metabolites play key roles in neurotransmission and energy metabolism, supporting their relevance to brain function.

Aims: To compare circulating metabolomic profiles related to low-grade inflammation and central energy metabolism in adolescents across the body mass index (BMI) spectrum.

Methods: A multicenter observational, cross-sectional study was conducted in 122 adolescents aged 10 to 17 years. Participants were classified according to BMI into three groups: low weight in the context of AN (n=47), normal weight (n=33), and obesity (n =42). Serum metabolomic profiling was performed using proton nuclear magnetic resonance spectroscopy. Measured variables included glycoprotein A (an emerging biomarker of chronic low-grade systemic inflammation), lipid fractions including omega-3 and polyunsaturated fatty acids, and metabolites involved in glycolysis, gluconeogenesis, and the Krebs cycle. Insulin resistance was estimated using the homeostatic model assessment. Continuous variables were compared using the Kruskal–Wallis test, while categorical variables were analyzed using the chi-squared/Fisher’s exact test. Correlations between BMI and metabolite levels were assessed using Spearman correlation coefficients.

Results: BMI differed significantly across groups (p<0.01). The low-weight group showed significantly lower concentrations of glycoprotein A (547 vs 612 vs 806 μM/L), glycoprotein B ( 285 vs 317 vs 400 μM/L), alanine (255 vs 311 vs 429 μM/L), glutamate (35.2 vs 56.6 vs 166 μM/L), tyrosine (40.5 vs 45.2 vs 59.5 μM/L), and leucine (81.6 vs 104 vs 135 μM/L). No significant differences were observed in glucose levels, whereas insulin resistance increased significantly across groups (0,87 vs 1,4 vs 4.99). BMI showed strong positive correlations with glycoprotein A (rs=0.71, p<0.001), insulin resistance ( (rs=0.72, p<0.001), glutamate (rs=0.75, p<0.001), and lactate (rs=0.74, p<0.001), and a strong negative correlation with omega-3 fatty acids (rs=-0.70, p<0.001).

Conclusions: The nutritional status spectrum in adolescence is associated with distinct metabolomic patterns reflecting differential regulation of inflammation and energy metabolism. In contrast to conditions characterised by chronic inflammatory activation, low weight in the context of anorexia nervosa was associated with reduced levels of inflammatory markers and broad decreases in metabolites involved in central metabolic pathways, consistent with previous findings suggesting altered inflammatory profiles in AN [4][5]. These alterations may be associated with neurobiological processes in AN, particularly those related to energy substrate availability and metabolic signalling. Clinical heterogeneity and the absence of dietary control represent important limitations. Given the cross-sectional design, causal inferences cannot be made.

References

  1. Schorr M, Miller K. The endocrine manifestations of anorexia nervosa: mechanisms and management. Nature Reviews Endocrinology. 2017.
  2. Hänsel A et al. Inflammation as a psychophysiological biomarker in chronic psychosocial stress. Neuroscience and Biobehavioral Reviews. 2010.
  3. Mayo-Martínez L et al. Unveiling metabolic phenotype alterations in anorexia nervosa through metabolomics. Nutrients. 2021.
  4. Dalton B et al. Inflammatory markers in anorexia nervosa: an exploratory study. Nutrients. 2018.
  5. Wu Y et al. Peripheral biomarkers of anorexia nervosa: a meta-analysis. Nutrients. 2024.