UC San Diego

Anorexia nervosa (AN) is an eating disorder characterized, in part, by aversion toward high-fat foods. Foods that are high in fats are major sources of fatty acids (FAs). FAs are crucial for brain health and have shown to be altered in psychiatric illnesses including eating disorders. The n-3 and n-6 FAs can undergo auto-oxidation or catalytic conversions in enzymatic pathways such as lipoxygenases (LOX), cyclooxygenases (COX), and cytochromes P450 (CYP) to form oxygenated metabolites termed oxylipins. Oxylipins formed by the Cytochrome P450 (CYP) enzymes are epoxy fatty acids, which are converted into diol fatty acids by soluble epoxide hydrolase (sEH). The genetic variants in the gene that encodes sEH, EPHX2, have been shown to be associated with AN risk. We studied the role of FAs and sEH pathway in AN using 50 AN cases and 47 control women. We have identified abnormal concentrations of several fatty acids at both fasting and postprandial timepoints in AN, a trend of elevated sEH activity and expression, and significant differences in several sEH-associated oxylipins in AN. These results confirm the n-3 PUFA-driven dysregulation in plasma PUFA, elevation of sEH in vivo and ex vivo, and aberrant oxylipins in AN. More studies with larger sample sizes are needed to confirm these findings and examine the mechanisms by which these dysregulations affect AN pathogenesis.