Metabolic pattern across energy imbalance: An exploratory metabolomics study of female body weight extremes including anorexia nervosa and athletes

In anorexia nervosa (AN), prolonged metabolic adaptation to severe energy deficiency can impair treatment efficacy. Similarly, low energy availability poses a recognized risk to athletes, potentially compromising health and performance. This cross‐sectional study aimed to characterize the plasma metabolic pattern of females with varying physical conditions, including AN patients, athletes, and normal weight, overweight and obese females. Non‐targeted metabolomics was applied to plasma samples from 107 females aged 18–40 years. Body fat was assessed via ultrasound and bioimpedance analysis. Nutritional intake, physical activity and clinical parameters were evaluated through standardized assessments. Sixty metabolites related to lipid, phospholipid and amino acid metabolism differed significantly between groups (ANOVA, false discovery rate q < 0.05). AN patients showed reduced long‐chain free fatty acids, medium‐chain acylcarnitines, etherphospholipids and branched‐chain amino acids (BCAAs) (Cohen's d < −0.5), alongside increased lysophospholipids and glycerophosphocholine ( d > 0.6). Athletes exhibited a similar though less pronounced pattern, with preserved BCAA levels, while overweight and obese individuals displayed opposing patterns. Metabolites including fatty acids, acylcarnitines, BCAAs and phospholipids positively correlated with body fat ( r s > 0.25, q < 0.05), whereas lysophospholipids and glycerophosphocholine correlated negatively ( r s < −0.25, q < 0.05). The metabolic pattern in AN may be consistent with metabolism alterations in energy‐deficiency states, which may be associated with structural tissue loss. Athletes demonstrated similar shifts that may reflect adaptive responses to potential low energy availability, while overweight and obese profiles were consistent with energy surplus. These findings emphasize associations of systemic metabolism adaptations in energy‐imbalance states and highlight the importance of adequate energy intake in vulnerable groups to maintain metabolic and structural integrity and prevent adverse health consequences.