Investigating the kynurenine pathway in pediatric metabolic health
Fatma Özgüç Çömlek1, Dilek Bingöl Aydın2, Fikret Akyürek3
1485663 Selçuk Üniversity, Medical Faculty, Pediatric Endocrinology , Konya, Türkiye.
Insights
Pediatric obesity alters tryptophan metabolism, with higher levels observed in obese children. The 3-hydroxykynurenine/kynurenine ratio correlated with metabolic syndrome indicators, suggesting a potential link.
Area of Science:
- Pediatric Endocrinology
- Metabolic Health
- Biochemistry
Background:
- Childhood obesity is a growing concern, linked to increased metabolic disease incidence.
- Tryptophan (TRP) metabolism, particularly the kynurenine pathway, is implicated in obesity-related inflammation.
- Indoleamine 2,3-dioxygenase (IDO) activity influences TRP catabolism and inflammatory processes.
Purpose of the Study:
- To investigate the impact of pediatric obesity on tryptophan metabolism.
- To explore the association between altered tryptophan metabolites and metabolic syndrome indicators in children.
- To assess changes in kynurenine pathway metabolites in relation to obesity severity.
Main Methods:
- Prospective cohort study of 86 children (≥10 years), including 56 obese participants.
- Obese children classified into obese and severely obese groups based on BMI percentiles.
- Serum kynurenine pathway metabolites analyzed using liquid chromatography-mass spectrometry/mass spectrometry.
Main Results:
- Obese children exhibited significantly higher plasma tryptophan levels compared to non-obese peers.
- The metabolite 3-hydroxykynurenine (3HK) and the 3HK/kynurenine (KYN) ratio were significantly elevated in obese children.
- Higher 3HK/KYN ratios correlated with increased triglycerides, GGT, HDL levels, and elevated systolic and diastolic blood pressure.
Conclusions:
- Pediatric obesity is associated with alterations in plasma kynurenine pathway metabolites.
- The 3HK/KYN ratio shows a correlation with key metabolic syndrome indicators in obese children.
- Further research with larger cohorts is necessary to confirm the link between these metabolites and metabolic syndrome in pediatric obesity.
Objectives:
The rise in obesity has led to a higher incidence of metabolic diseases in children. Overnutrition leads to increased intake and availability of tryptophan (TRP). Research indicates a link between indoleamine 2,3-dioxygenase (IDO) activity, the activation of the tryptophan catabolic pathway, and inflammation associated with obesity. This study investigated how pediatric obesity affects tryptophan metabolism and its potential link to metabolic syndrome.
Methods:
This prospective cohort study included 86 children aged 10 years and older, 56 of whom were obese. Obese children with body mass index (BMI) >95th percentile were divided into two groups: obese (BMI greater than 120 % of the 95th percentile for age and sex) and severely obese (BMI greater than 140 % of the 95th percentile for age and sex). Serum levels of kynurenine pathway metabolites were determined by liquid chromatography-mass spectrometry/mass spectrometry system.
Results:
The mean ages (13.6 and 13.2 years) and gender distribution (36.7 and 46.2 % male) were similar across the groups. There were significant differences in tryptophan levels between the groups, being higher in the obese groups (p<0.001). 3-hydroxykynurenine (3HK) was significantly higher in the obese group (p=0.029). 3-hydroxykynurenine/kynurenine (3HK/KYN) ratio also significantly correlated with increased GGT and triglyceride levels and low HDL. Also higher 3HK/KYN ratio was correlated with elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels. No significant relationship was found between the KYN/TRP ratio and obesity metabolic syndrome indicators.
Conclusions:
Although plasma kynurenine pathway metabolites showed some changes in children with obesity, larger series studies are needed to determine the relationship with metabolic syndrome.
More Related Videos
07:04A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats
Published on: August 19, 2018
07:26Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
Published on: January 26, 2012
Related Concept Videos
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Inborn Errors of Metabolism
Biosynthesis of Nucleic Acids
Pharmacokinetics in Pediatric Patients: Drug Excretion
Regulation of Metabolism
Amino Acid Biosynthetic Pathways
