Unveiling Metabolic Phenotype Alterations in Anorexia Nervosa through Metabolomics

Abstract

Anorexia nervosa (AN) is a mental disorder characterized by an intense fear of weight gain that affects mainly young women. It courses with a negative body image leading to altered eating behaviors that have devastating physical, metabolic, and psychological consequences for the patients. Although its origin is postulated to be multifactorial, the etiology of AN remains unknown, and this increases the likelihood of chronification and relapsing. Thus, expanding the available knowledge on the pathophysiology of AN is of enormous interest. Metabolomics is proposed as a powerful tool for the elucidation of disease mechanisms and to provide new insights into the diagnosis, treatment, and prognosis of AN. A review of the literature related to studies of AN patients by employing metabolomic strategies to characterize the main alterations associated with the metabolic phenotype of AN during the last 10 years is described. The most common metabolic alterations are derived from chronic starvation, including amino acid, lipid, and carbohydrate disturbances. Nonetheless, recent findings have shifted the attention to gut-microbiota metabolites as possible factors contributing to AN development, progression, and maintenance. We have identified the areas of ongoing research in AN and propose further perspectives to improve our knowledge and understanding of this disease.

Keywords: anorexia; mass spectrometry; metabolic phenotype; metabolism; metabolomics; microbiota.

Figure 1

Main factors predisposing to the development of anorexia nervosa [21,22].

Figure 2

Summary of the main metabolomic alterations found in plasma or serum samples from AN patients in the included studies. Altered pathways: (A) glycolysis and gluconeogenesis, (B) methionine and cysteine metabolism, (C) serine and glycine metabolism, (D) lipid metabolism, (E) urea cycle, (F) tricarboxylate cycle, (G) phenylalanine and tyrosine metabolism, (H) glutamate, glutamine, proline and histidine metabolism, (I) branched-chain amino acids metabolism, (J) serotonin pathway, (K) kynurenine pathway, (L) indole pathway, (M) tryptophan metabolism. Metabolites: (1) glucose, (2) pyruvate, (3) alanine, (4) taurine, (5) serine, (6) glycine, (7) methionine, (8) citrate, (9) cis-aconitate, (10) isocitrate, (11) succinate, (12) malate, (13) asparagine, (14) ornithine, (15) arginine, (16) guanidinosuccinate, (17) p-cresyl sulfate, (18) tyrosine, (19) phenylalanine, (20) phenylacetylglutamine, (21) phenylacetate, (22) hippurate, (23) tryptophan, (24) indole-3-acetate, (25) indoxyl sulfate, (26) glutamate, (27) glutamine, (28) histidine, (29) proline, (30) fatty acids, (31) phosphatidylcholines, (32) lysophosphatidylcholines, (33) sphingomyelins, (34) acylcarnitines, (35) oxylipins, (36) leucine, (37) isoleucine.