Abstract
Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. This study aimed to investigate alterations in KYN and microbiota-mediated indole routes of TRP metabolism in obese subjects relatively to non-obese controls and to determine their relationship with systemic inflammation.Methods: Eighty-five obese adults (avg. BMI = 40.48) and 42 non-obese control individuals (avg. BMI = 24.03) were recruited. Plasma levels of TRP catabolites were assessed using Ultra High Performance Liquid Chromatography-ElectroSpray-Ionization-Tandem Mass Spectrometry. High-sensitive C-reactive protein (hsCRP) and high-sensitive interleukin 6 (hsIL-6) were measured in the serum as markers of systemic inflammation using enzyme-linked immunosorbent assay.Results: Both KYN and microbiota-mediated indole routes of TRP metabolism were altered in obese subjects, as reflected in higher KYN/TRP ratio and lower 5-HT and indoles levels, relatively to non-obese controls. HsIL-6 and hsCRP were increased in obesity and were overall associated with TRP metabolic pathways alterations.Conclusion: These results indicate for the first time that KYN and indole TRP metabolic pathways are concomitantly altered in obese subjects and highlight their respective associations with obesity-related systemic inflammation.
Highlights
Obesity is a metabolic disorder characterized by a chronic low-grade inflammatory state, as reflected in increased levels of circulating inflammatory markers, including pro-inflammatory cytokines and the acute phase protein C-reactive protein (CRP) [1,2,3,4]
A growing body of evidence indicates that inflammation is associated with alterations in the metabolism of tryptophan (TRP) [12, 13], an essential amino acid and biochemical precursor of serotonin (5-HT), kynurenine (KYN) and indoles [14]
Alterations in TRP metabolism in obese subjects may arise from the gut microbiota, which has been shown to be disrupted both at compositional and functional levels in obesity [20,21,22]
Summary
Obesity is a metabolic disorder characterized by a chronic low-grade inflammatory state, as reflected in increased levels of circulating inflammatory markers, including pro-inflammatory cytokines and the acute phase protein C-reactive protein (CRP) [1,2,3,4]. IDO is responsible for the catabolism of TRP along the KYN pathway, likely resulting in reduced 5-HT synthesis Consistent with this notion, activation of the KYN pathway has been documented in several studies conducted in obese subjects [16,17,18,19]. Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. This study aimed to investigate alterations in KYN and microbiota-mediated indole routes of TRP metabolism in obese subjects relatively to non-obese controls and to determine their relationship with systemic inflammation
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