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Objective: To study the plasma lipidome of patients with anorexia nervosa (AN) before and after weight restoration treatment and report associations with AN subtypes and oral contraceptive pill (OCP) usage.

Methods: Quantitative shotgun lipidomics analysis was used to study plasma lipids of 50 female patients with AN before and after weight restoration treatment and 50 healthy female controls (HC). The AN group was assessed with blood samples and questionnaires before and after weight restoration. Results: In total we quantified 260 lipid species representing 26 lipid classes of which

13 lipid class concentrations were elevated in patients with AN at admission compared with HC. Lipid classes remained elevated after weight restoration treatment of 84 days (median; interquartile range 28), and only the concentration of the ceramide lipid class increased between pre- and post-treatment (p =.03), whereas lysophosphatidylcholine (LPC, p =.02), ether-linked Phosphatidylcholine (LPCO, p =.02), and lysophosphatidylethanolamine (LPE, p =.009) decreased.

Conclusion: In AN, 13 out of 26 lipid class concentrations were elevated at admission and remained elevated post-treatment. Ceramides increased further between pre- and post-weight restoration treatment, which could be related to the rapid weight gain during re-nutrition. Further research is needed to elucidate the effects of weight restoration treatment on short- and long-term lipid profiles in individuals with AN.

Public Significance Statement: Lipidomics research can increase the understanding of AN, a complex and potentially life-threatening eating disorder. By analyzing lipids, or fats, in the body, we can identify biological markers that may inform diagnosis and develop more effective treatments. This research can also shed light on the underlying mechanisms of the disorder, leading to a better understanding of the processes involved in eating behavior.