Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity.

Julia Lischka,Andrea Schanzer,Charlotte De Gier,Margot Baumgartner,Maximilian Zeyda,Susanne Greber-Platzer

doi:10.3390/nu14020286

Abstract

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.

Highlights

The dramatic increase in pediatric obesity foreshadows the substantial burden of noncommunicable disease that will strain the health care and social systems in the future [1,2,3,4].Comorbidities associated with obesity include cardiovascular diseases, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia [5,6,7].Though obesity and the development of non-communicable diseases are closely associated [8,9], a higher BMI is not necessarily indicative of worse metabolic health
Our explorative study shows that within a high-risk population of pediatric patients with severe obesity, BMI z-score and body fat mass are associated with a shift in tryptophan catabolism, leading to increased breakdown towards the kynurenine pathway and decreased catabolism along the serotonin pathway
The shift from serotonin to kynurenine synthesis observed in our study is already well-known as the “serotonin hypothesis,” which proposes this shift as a vicious cycle in the etiology of depression. We show that this known dysregulation in tryptophan catabolism may be a factor in metabolic diseases [53,54]

Summary

Introduction

The dramatic increase in pediatric obesity foreshadows the substantial burden of noncommunicable disease that will strain the health care and social systems in the future [1,2,3,4].Comorbidities associated with obesity include cardiovascular diseases, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia [5,6,7].Though obesity and the development of non-communicable diseases are closely associated [8,9], a higher BMI is not necessarily indicative of worse metabolic health. The dramatic increase in pediatric obesity foreshadows the substantial burden of noncommunicable disease that will strain the health care and social systems in the future [1,2,3,4]. Comorbidities associated with obesity include cardiovascular diseases, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia [5,6,7]. Though obesity and the development of non-communicable diseases are closely associated [8,9], a higher BMI is not necessarily indicative of worse metabolic health. The underlying pathomechanisms, considering divergent obese phenotypes, remain enigmatic. Understanding the various mechanisms of how obesity affects metabolic health is essential to developing effective prevention and treatment strategies, in youth [10,11].

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