Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation

• Published in: Frontiers in immunology Vol. 11; pp. 557 - 7
• Main Authors: Cussotto, Sofia, Delgado, Inês, Anesi, Andrea, Dexpert, Sandra, Aubert, Agnès, Beau, Cédric, Forestier, Damien, Ledaguenel, Patrick, Magne, Eric, Mattivi, Fulvio, Capuron, Lucile
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 15.04.2020; Frontiers Media S.A
• Subjects: Adult; Female; Humans; Immunology; indoles; inflammation; Inflammation - immunology; Inflammation - metabolism; kynurenine; Kynurenine - metabolism; Life Sciences; Male; Metabolic Networks and Pathways - immunology; obesity; Obesity - immunology; Obesity - metabolism; tryptophan; Tryptophan - metabolism; indoles; kynurenine; inflammation; obesity; tryptophan; This article was submitted to Inflammation; a section of the journal Frontiers in Immunology obesity
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00557

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. 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. 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. 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.