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.

Fatigue is frequent in patients with diabetes and this symptom appears to be more prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. This possibility was assessed in a sample of 20 type 2 diabetic patients relatively to a group of 20 type 1 diabetic subjects. Specific dimensions of fatigue, including general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation, were assessed using the Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the measurement of serum inflammatory markers [high-sensitive C-reactive-protein (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis-factor-α (hsTNF-α) and neopterin]. Clinical parameters including indexes of adiposity were collected. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions of general fatigue, physical fatigue and reduced activity, together with greater levels of inflammatory markers that correlated with indexes of adiposity. Regression analyses controlling for diabetes duration, insulin treatment status, glycemic control and fasting status, indicated that levels of inflammatory markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that adiposity did not significantly account for the relationship of inflammatory markers with fatigue scores albeit coefficient regressions decreased somewhat when this variable was controlled for in regression models. These findings indicate that systemic low-grade inflammation relates to fatigue symptoms in patients with type 2 diabetes and suggest the involvement of inflammatory processes in the pathophysiology of diabetes-related fatigue.