Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa–Exploratory Study

Abstract

The link between the kynurenine pathway and immunomodulatory molecules—fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)—in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases (KAT1-3) were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered. The expression of the gene encoding KAT3, but not of genes encoding KAT1 and KAT2 (measured in blood mononuclear cells), was higher in patients with AN. In AN, fractalkine positively correlated with TRP, while sICAM-1 was negatively associated with 3-OH-KYN and positively linked with the ratio KYN/3-OH-KYN. Furthermore, TRP and fractalkine were negatively associated with the body mass index (BMI) in AN. Expression of KAT1, KAT2 and KAT3 did not correlate with fractalkine, sICAM-1 or BMI, either in AN or control. Increased fractalkine may be an independent factor associated with the restrictive type of AN. Excessive physical activity probably underlies increased expression of KAT3 observed among enrolled patients. Further, longitudinal studies on a larger cohort of patients should be aimed to clarify the contribution of fractalkine and KAT3 to the pathogenesis of AN.

SLC6A4 DNA Methylation Levels and Serum Kynurenine/Tryptophan Ratio in Eating Disorders: A Possible Link with Psychopathological Traits?

“…In the presence of low fat stores, depleted glycogen, and insufficient Kcal intake, AN patients have to turn to release amino acids from the skeletal muscle back into the plasma. In the middle of these opposite results, other studies demonstrated that plasma Trp levels did not change comparing underweight AN patients and CTRs [ 56 ]. In our cohort, higher Trp value was registered for restricting and purging AN subtypes as well as BN patients and was positively correlated with excessive levels of physical activity, corroborating the catabolism hypothesis.…”

New Perspective on Anorexia Nervosa: Tryptophan-Kynurenine Pathway Hypothesis

“…Likewise, a cross-sectional study including 59 dialyzed patients, of which 13 manifested poor appetite and malnutrition, revealed that the plasma levels of free TRP, LNAA, and TRP/LNAA ratios were similar between anorectic and well-nourished patients [ 45 ]. Similarly, a study of 20 female patients with restrictive AN revealed no changes in serum TRP compared to 24 control individuals [ 53 ].…”

“…KYNA deficiency normalized as the body weight increased [ 52 ]. A quarter of a century later, the peripheral levels of kynurenines were investigated in 20 female patients with restrictive AN (mostly drug-free, all during the first episode of the disease) and compared with 24 controls [ 53 ]. We detected neither changes in serum L-kynurenine, KYNA, nor in the ratios TRP/L-kynurenine or L-kynurenine/KYNA.…”

“…Neither 3-OH-kynurenine levels nor L-kynurenine/3-OH-kynurenine and KYNA/3-OH-kynurenine ratios were altered in the serum of 20 females with restrictive AN [ 53 ]. In 10 medication-free female patients with AN, CSF QUIN levels were within the control range, yet the ratio QUIN/KYNA was significantly higher during the underweight phase of AN [ 52 ].…”

“…The expression of mRNA for KAT1–3 was studied in 20 female patients with restrictive AN and in 24 controls [ 53 ]. The expression of the gene encoding KAT3 , but not of the genes encoding KAT1 and KAT2, was higher in 20 patients with restrictive AN.…”