Perturbations in plasma amino acid and lipoprotein subfraction profiles in anorexia nervosa before and after refeeding: A metabolomic cross-sectional and longitudinal analysis

Abstract

Background

Anorexia nervosa (AN) is a life-threatening eating disorder, which is increasingly being considered a metabo-psychiatric condition. We aimed to assess how the lipoprotein subfraction and plasma metabolome are altered in acutely underweight patients with AN (AcAN), if they change with short-term weight-restoration, and whether these changes point towards altered cardiometabolic risk.

Methods

Using nuclear magnetic resonance spectroscopy, we measured and compared the plasma concentrations of 132 metabolites, aminoacids and lipoprotein subfractions in young female patients with AcAN before (n = 72) versus after (n = 46) a short-term inpatient refeeding program resulting in weight-restoration (longitudinal analysis), as well as versus female healthy control (HC) participants of similar age (n = 74) (cross-sectional analysis).

Findings

Patients with AcAN showed elevated plasma cholesterol levels due to higher concentrations of small and dense Low Density Lipoprotein (LDL-6) and of large and less dense High Density Lipoprotein (HDL-1) subfractions compared to HC. Additionally, they had lower plasma concentrations of branched chain amino acids and glucose and higher concentrations of the gluconeogenic amino acids glutamine, alanine and methionine. Refeeding elevated the plasma cholesterol levels further, but with a different pattern compared to AcAN, by increasing the concentrations of the larger and less dense LDL (LDL-1, LDL-2, LDL-3) particles and of smaller and more dense HDL (HDL-2, HDL-3) subfractions. However, refeeding only partially restored the amino acid concentrations.

Conclusion

Lipoprotein profiles in AcAN point towards a potentially elevated risk for atherosclerosis; an altered lipoprotein profile was also detected after refeeding. Metabolite profiles in AcAN indicate an advanced catabolic state with only partial restoration after refeeding.